Since there appears to be interest in this news group on growth hormone
here is the report submitted by Robert Cohen to the FDA in an effort to
revoke its use. The insulin growth factor is increased, the regulator of
cancer, and spleen size was increased as much as 46% in lab animals, a pre-
leukemic condition. An explosion in leukemia and cancer is expected.
Anyone wanting more information can call Robert Cohen at 1 201-599-0325.
Domain: betty at pd.org
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Recombinant bovine somatotropin (rBST) increases levels
of insulin-like growth factor (IGF) in milk; IGF in milk
is orally active; IGF is a key factor in the growth and
survival of cancer in animals and humans.
This paper was presented to the FDA on April 21, 1995 at the
Invitation of Dr. Stephen Sundlof, Director of the Center for
Veterinary Medicine, as a Result of a Citizen Petition Filed by
Robert Cohen (94P-03431CP1) 9/16/94.
Attending that Meeting for FDA were:
1) Dr. Richard Teske
2) Dr. Robert Condon
3) Dr. John Leighton
4) Dr. William Marnane
5) Mr. Robert Sauer
Fourth Draft Robert Cohen
April 20, 1995
AS A RESULT OF THAT MEETING FDA:
1) Believes that after cows are treated with BST there *is* an
increase in IGF levels in milk.
2) Believes that some IGF bypasses digestion and is absorbed intact
by the intestinal lumen.
3) Believes that although IGF levels in milk increase after BST
treatment and although some quantities of IGF survive digestion, IGF
is *not* orally active. Neither are similar milk hormones.
Therefore, while nursing mothers have biological effects from
hormones and human breast feeding might have psychological benefits
for the infant, but it is not possible for there to be hormonal
4) Agrees to rigorously review all of the references and data in
this article and to re-examine the data cited in the unpublished
reports cited as references in the Juskevich and Guyer article.
RECOMBINANT BOVINE SOMATOTROPIN (rBST) INCREASES LEVELS
OF INSULIN-LIKE GROWTH FACTOR (IGF) IN MILK; IGF IN MILK
IS ORALLY ACTIVE; IGF IS A KEY FACTOR IN THE GROWTH AND
SURVIVAL OF CANCER IN ANIMALS AND HUMANS.
The Food and Drug Administration (FDA) approved the use of a
genetically engineered version of bovine somatotropin (rBST) after a
process which represented the most researched and controversial food
and drug application in history. This paper will explore three major
1) The data presented to FDA was not rigorously reviewed,
was presented in a biased manner and the actual product
which was approved by FDA was significantly different
than the actual product in use today.
2) Numerous tests including toxicology studies were not
performed because it was pre-determined that there
could be no biological effects upon animals or humans
from oral ingestion of rBST or IGF. This conclusion
was made because of a belief that strong digestive
enzymes would destroy milk hormones. This paper will
demonstrate that milk is an enzyme inhibitor and that
hormones survive digestion.
3) IGF is a key factor in the growth and survival of
tumors in humans. IGF is a proliferative growth
hormone which increases after cows are treated with BST.
Milk and dairy products are staples in the American diet and
represent the largest food industry in the United States. To
increase milk output of cows, scientists have genetically engineered
bovine growth hormone through DNA technology and have developed a
substance which was meant to be similar to a cow's normally occurring
Through the use of genetic engineering technology the bacterium, E.
coli, received the gene that enabled it to produce a synthetic
version of the natural bovine growth hormone.
A GENE TRANSCRIPTION ERROR
Monsanto (1) has admitted that an unusual amino acid was created by
their new technology. Amino acid #144 which should have been lysine
has been replaced on the normal chain with epsilon-N-acetyllysine.
Monsanto's publication did not indicate how long (after rBST was
introduced into milk in 1990) this unusual amino acid has been
consumed by the American milk drinking public.
DATA WAS NEVER PROPER REVIEWED
The FDA and Monsanto, manufacturer of rBST, collaborated on a paper
(2) which was published in "Science." This article was intended to
end the controversy surrounding rBST. As a result of this article,
the Journal of The American Medical Association and the National
Institutes of Health endorsed rBST use. Evidence exists that the
data in that article were not reviewed by the NIH or JAMA.
Unpublished reports were cited but never made available for peer
review. By not making available actual data for tissue and organ
weights of subjects treated with genetically engineered hormones,
peer review was compromised. References were requested through the
Freedom of Information Act office but Monsanto cites "trade
protection" and hides behind a protective veil.
ACTUAL REFERENCES NEVER PEER REVIEWED
>From the Juskevich and Guyer paper:
REF. # 40 is an unpublished Upjohn report.
REF. # 41 is an unpublished Hazleton Lab report.
REF. # 42 is an unpublished Searle report.
REF. # 43 is an unpublished American Cyanamid report.
REF. # 44 is an unpublished Eli Lilly report.
REF. # 70 is an unpublished Elanco report.
It is clear that these reports are shared by Monsanto competition.
Trade protection should not be reason to deny a researcher access to
reports cited as references.
BST-TREATED MILK DIFFERS FROM UNTREATED MILK
The Juskevich and Guyer paper contradicts the conclusion reached by
FDA, NIH and the World Health Organization. All agree that milk from
rBST-treated cows is indistringuishable from the milk of non-treated
cows. Their conclusion contradicts the actual data presented. The
"Recombinant bGH treatment produces an increase in the
concentration of insulin-like growht factor-I (IGF-I)
in cow's milk"
Data in the Juskevich paper suggest that there are indeed biological
effects from oral ingestion of rBGH on laboratory animals. Animals
reacting to subcutaneous injections demonstrated significantly large
and abnormal spleen growth rates (as compared to the control group).
>From table #2 on page 878 we note that the typical male spleen
increased in size 39.6% while the female spleen grew 46%. Those
doing the research had to note these dramatic numbers and had to have
observed the spleen effects from oral ingestion.
REPRINTED FROM "SCIENCE" - AUGUST, 1990, PAGE 878
Table 2 Absolute organ weights (in grams) in control rats and
rbGH-treated rats (means +/- SD). Charles River CD rats (n=30 rats
per sex) were treated for 90 days with rbGH either by gavage or by
subcutaneous administrations, and one group of animals served as
untreated controls. From (42) with permission. c 1989 Monsanto
Organ Subcutaneous Oral
0 1.0 0.1 0.5 5.0 50.0
Kidneys 3.677 4.188 3.178 3.695 3.540 3.544
Liver 16.549 20.364 15.614 15.740 15.993 15.098
Heart 1.726 1.941 1.645 1.608 1.618 1.640
Spleen 0.912 1.274 0.910 1.051 0.987 1.002
Kidneys 2.067 2.464 2.040 2.170 2.102 2.025
Liver 8.637 11.146 8.302 8.754 8.446 8.297
Heart 1.041 1.215 1.061 1.101 1.034 1.070
Spleen 0.585 0.855 0.601 0.663 0.630 0.608
Let use examine what occurs to the animals (mean averages):
1) subcutaneous males gained 39.69% spleen weight
2) subcutaneous females gained 46.15% spleen weight
3) oral males gained 8.33% spleen weight
4) oral females gained 6.92% spleen weight
The subject animals in this study were sacrificed after 90 days.
Scientists at the Albert Einstein College of Medicine found that mice
treated with IGF-II developed a diverse spectrum of tumors at a
higher frequency than controls after 18 months of age. This long
latent period before tumors arise and the wide spectrum of tumor
types suggest that IFG may function primarily as a tumor progression
factor in mice via autocrine and endocrine mechanisms of action. (3)
There is evidence of such latent effects in Juskevich. Data is
presented in a remarkably biased manner:
TABLE #1 (PAGE 877) Body weight changes (in grames) of control rats
and rbGH-treated rats (means +/- SD). Charles River CD rats were
treated for 90 days with rbGH either by gavage or by subcutaneous
injection; and one group of animals served as untreated controls.
>From (42) with permission c 1989 Monsanto Agricultural Company.
(AUTHOR'S NOTE: I HAVE PRINTED ONLY THE CONTROL GROUP AND
SUBCUTANEOUS GROUP WEIGHTS TO ILLUSTRATE THE POINT OF DATA
MANIPULATION BY THE MONSANTO/FDA PUBLICATION)
MALES (CONTROL) (SUBCUTANEOUS)
8 58 +/- 8.5 72 +/- 20.4
29 170 +/- 20.3 207 +/- 34.5
50 239 +/- 29.8 294 +/- 44.8
85 324 +/- 39.2 432 +/- 60.3
FEMALES (CONTROL) (SUBCUTANEOUS)
8 24 +/- 8.7 33 +/- 6.5
29 81 +/- 12.0 101 +/- 13.6
50 110 +/- 16.6 150 +/- 18.9
85 148 +/- 24.4 217 +/- 32.3
The average weight gains for subcutaneous animals (per time period)
are 20-30 percent greater than the control group. Look closely at
the parameters. Is this a standard chart? Day 8, day 29, day 50,
and day 85? Did the data simply fit neatly into these designated
Let's examine what occurs to the animals between days 50 and 85. The
average male gains 62% more weight than the control male during that
period. The average female gains 76% more than the average control
This is a very clever non-presentation of data. There is indeed a
dramatic latency growth spurt that occurs at some time two months
after initial introduction of the hormone.
It would be interesting to do statistical analysis on all of the
subject cited in the Juskevich article, but alas, FDA and MONSANTO
will not release such data, citing the privilge of protection from
exclusivity of "trade secrets."
No oral effects? In addition to the average male (TABLE 2) gaining
(from oral ingestion) 8.33% in his spleen weight, the average female
gains 6.92%. The average male also loses 5.10% kidney weight, loses
5.6675% liver weight, and loses 5.6925% heart weight (when compared
to the control group). These are biological effects! Are they
statistically significant? We may never know, because freedom of
information act requests are not enough to induce FDA or Monsanto
into releasing data necessary to perform such analyses. (Requests by
this author have been denied.)
IGF - CELL PROLIFERATION AND CANCER
Should IGF (insulin growth factor) be such a concern? Hammond and
Collier, writing for Monsanto Agricultural Company (4) state:
"Based upon the no effect levels determined in rat
gavage studies (oral ingestion of rBGH), it is possible
to approximate safety factors for ingestion of these two
proteins (sometribove and IGF-I). However, estimation of
safety factors for sometribove (BST,rbGH) consumption is
not necessary, since it would not be hormonally active in
humans even if it could be absorbed. IGF-I is not orally
active in laboratory animals supporting a large margin of
safety for their consumption."
The most recent research would tend to support the dramatic role that
IGF plays in cellular growth. Keinman (5) report that IGF-I is found
to be involved in the growth regulation of endometrial tumor cells
and is 30-fold more potent than insulin, suggesting that the effects
of these growth factors are mediated by the IGF-I receptor. D'Errico
(6) notes that results obtained using molecular biology techniques
suggest a possible role for insulin-like growth factor II (IGF-II) in
the pathogenesis of hepatocellular carcinoma (HCC). Kowk (7) has
found that the biological effects of IGF-I are initiated by its
binding to the IGF-I receptor, which is able to transduce mitogenic
and metabolic signals, supporting the hypothesis that the IGF-I
receptor is involved in the development of diabetic vascular
complications. Wimalasena (8) found IGF-I to increase cell growth,
and a maximal effect of 3-5 fold increase in cell number was
There is evidence that IGF functions on a nanomolecular level. MCF-7
cancer cells proliferate in response to nanomolar concentrations of
IGF-I and IGF-II. De-Leon (9) reported that the actions of both
peptides are mediated through the IGF-I receptor concluding that
IGF-I and IGF-II are potent mitogens in MCF-7 cells and can stimulate
cell proliferation through all three receptors. Martin (10) reports
that IGF-II stimulates cell proliferation via the type I IGF
receptor. The type I IGF receptor mediates IGF-II induced autocrine
neuroblastoma cell growth.
Ambrose (11) observed that the interaction of insulin-like growth
factors with the IGF-I receptor is an important step in the control
of cell proliferation and development. In particular, IGF-I and
IGF-II are key regulators of central nervous system development and
may modulate the growth of glial tumors. Nielsen (12) noted that the
transcription of IGF-II genes lead to the production of significant
amounts of IGF-II which stimulate the proliferation of MSRCT
(cancerous growths) by interaction with IGF-I receptors on the cells.
FDA, based upon Monsanto's research, continues to proclaim that IGF
in milk has no effect on human metabolism. IGF-I is a mitogenic
growth factor. Prager (13) found rat cells responding to in vitro
IGF-I treatment by increased proliferation and DNA synthesis. Tumor
cell assays confirmed continued expression of IGF-I receptors. Raile
(14) observed similar effects. Insulin-like growth factor I and II
were implicated in the growth promotion of in vivo tumors and tumor
cells in vitro. Tumor cells responded to an addition of exogenous
insulin growht factor with an increase of DNA synthesis.
Langford (15) found that IGF-I has multiple metabolic actions and
effects on the differentiation and proliferation of a wide variety of
IGF IN MILK SURVIVES DIGESTION
FDA continues to accept the premise made by Monsanto that IGF-I is
degraded by digestive enzymes and is not active in the upper
gastrointestinal tract. FDA's conclusion is echoed by most respected
Yet, according to Olanrewaju, recently published in the "American
Journal of Physiology," infusion of IGF in rats (in levels similar to
those in bovine milk) increases the cellularity of the intestinal
mucosa. (16) Data indirectly supports the hypothesis that dietary
IGF-I may be absorbed. This was supported by Baumrucker at the
Department of Dairy and Animal Science at Pennsylvania State
University (17) who wrote that dietary IGF-I may be absorbed and
causes transient systemic effects in the newborn calf.
Taylor (18) reports that insulin-like growth factors have a potent
mitogenic action on the bowel.
Playford (19) reports that milk proteins prevent digestion of luminal
growth factors, allowing them to stimulate intestinal growth. Casein
acts as an enzyme inhibitor. Unlike IGF-I in serum, IGF-I secreted
into the gastrointestinal lumen is not bound to insulin-like growth
factor I binding proteins. Since the growth factor is not protein
bound, its concentration in the gut lumen may be high enough to exert
biological activity. IGF is actually abserbed in a similar manner to
EGF and passes through the digestive system undigested.
Rat milk soluble fraction (RMSF) protects milk borne peptides in the
gastrointestinal lumen by inhibiting in vitro the luminal
peptidolysis, according to Rao. (20)
Oster (21) presented evidence that bovine xanthine oxidase is
entrapped in liposomal form by the milk homogenization process. In
this form, milk resists gastric digestion and becomes biologically
available. As a result of unnatural micronization (homegenization)
the number of fat globules are increased and the size of those
globules reduced. This enhances hormonal carrier potential and the
permeability of intestinal mucosa increases as does hormonal
FDA is incorrect in assuming that IGFs are broken down in the gut,
and therefore cannot affect animal or human metabolic functions. The
evidence overwhelmingly contradicts this conclusion.
NATURALLY OCCURRING IGF IN THE HUMAN BODY
Human blood and saliva does contain IGF-I. That IGF-I is bound to
proteins and receptors, and are building components of cellular
material. An analogy must be made to the levels of IGF-I present in
the human body. If one were able to analyze the average home, on
could make the statement that the home contained a 55 gallon drum of
glue. One could not walk through the house and find that glue; it
would be present in the carpet, sheetrock, tiles, furniture, etc. If
an individual walked into that house with a bucket of free flowing
un-bound glue, splashing that bucket as he walked through the house,
he would be creating great damage.
Free IGF-I works the same way. The actual levels of free IGF-I are
relatively quite small. They have been measured most recently by
Frystyk (22) who found that IGF-I levels in humans were inversely
proportional to age ranging from 950 ng/L (20-30 yrs. of age) to 410
ng/L (60+ yrs. of age). Levels of IGF-II were independent of age,
being 1480 ng/L.
SYNERGISM OF IGF WITH OTHER HORMONES
The mediating effects of IGFs appear to be greatly enhanced and are
synergistic when combined with other factors. Kachra (23) found that
when glucagon and GH are combined with rBGH (50 mg/ml), they
augmented increased levels of IGF-I up to 12-fold.
Frodin (24) demonstrated that the combined effect of IGFs and bFGF is
synergistic. The degree of synergism was 2-4 fold in neonatal
chromaffin cells and 10-20-fold in adult chromaffin cells compared
with the effect of each growth factor alone. IGF-I and IGF-II acted
in synergy with bFGF to stimulate proliferation and survival of
chromaffin cells. Romagnolo (25) found that the induction of IGF-I
cells with dexamethasone (DEX) triggered a 29.5-fold increase in the
secretion of IGF-I.
IGF AND CANCER
IGF-I and II have been identified as autocrine and endocrine growth
regulators which accelerate various types of carcinomas. IGF-I is
considered to play an important role in the proliferation of
pancreatic cancer cells, according to Gillespie (26).
Glick (27) noted that IGFs play an important role in the regulation
of glucose metabolism in CNS tumors.
It was reported by Atiq that insulin-like growth factor II is
associated with human primary colorectal tumors and colin-carcinoma
cell lines. (28)
Yashiro (29) found IGF-bp activity was significantly higher in cancer
extracts, suggesting that higher IGF-bp activity in cancer tissue is
involved in regulating growth of thyroid papillary carcinoma cells.
Robbins (Genentech, Inc.) found that IGF-I increased lymphocyte
numbers in all of the peripheral lymphoid organs examined. This
increase had functional significance, and Robbins concluded that
IGF-I produced locally by thymic and bone marrow cells may be a
natural component of B and T cell lymphopoiesis. (30)
Yun demonstrated that IGF transcripts were 32-64-fold more abundant
in Wilms tumors than in the adjacent uninvolved kidneys. IGF-II is
suggested as playing a role in transforming growth factor in Wilms
Minniti concluded that insulin-like growth factor II (IGF-II) acts as
an autocrine growth and motility factor in human rhabdomyosarcoma
cell lines. Analyses of tumor biopsy specimens demonstrate high
levels of IGF-II mRNA expression. All tumor specimens examined
expressed the gene for IGF-II, to surrounding stroma. These data
suggest that the IGF-II autocrine loop may be operating not only in
vitro but also in vivo. (32)
Developing osteogenic sarcoma were researched by Kappel who wrote
that this type of cancer is the most common bone tumor of childhood
and typically occurs during adolescent growth spurts when growth
hormone and insulin-like growth factor-I (IGF-I) may be at their
highest lifetime levels. He noted that human osteogenic sarcoma cell
lines are dependent on signaling through IGF-I receptors for in vitro
survival and proliferation. Furthermore, they suggest modulation of
the growth hormone IGF-I axis may affect the growth of these tumors
in vivo. (33)
Lippman, as early as 1991, had implicated IGF-I as being critically
involved in the aberrant growth of human breast cancer cells. (34)
Lee (35) observed the processing of insulin-like growth factor by
human breast tissue and commented:
"This indicates, for the first times, that oestrogen
regulation of IGF-I peptide in breast cancer cells
would support the hypothesis that IGF-II has and
autocrine regulatory function in breast cancer."
Chen (36) noted that IGFs are potent mitogens for malignant cell
proliferation in the human breast carcinoma cell line.
Figueroa confirmed that insulin-like growth factors (IGFs) are potent
mitogens for breast cancer cells and their activity is modulated by
high affinity binding proteins. (37)
Li (38) treated breast cancer cells (MCF-7) with IGF-I and observed a
10-fold increase in mRNA levels of cancer cells and concluded that
IGF-I modulation of gene expression appears to be an important step
in cellular proliferation. Krasnick (39) furnishes another clue to
this puzzle by revealing that IGF-I may have a role in the regulation
of human ovarian cancer. His data support a role for IGF-I in
proliferation of ovarian cancer and suggests that IGF-I and estradiol
interact in a synergistic manner and regulate this malignancy.
Musgrove (40) states that growth factors play a major role in the
control of human breast cancer cell proliferation.
THE MISSING LINK
On November 8, 1994, the New York Times published a store (written by
Gina Kolata) (41) which revealed:
1) There is good reason to believe that many very early cancers
never become clinically significant.
2) Although 1% of women between the ages of 40 and 50 are
diagnosed with breast cancer, autopsy studies reveal that
39% of women in that age group have tumors in their breasts.
3) Forty-six percent of men between the age of 60 and seventy
have prostate cancer although only 1% are clinically
4) Virtually all people over 50 have thyroid tumors.
5) Cancerous tumors are the ones that have somehow thrown off
the usually tight genetic controls on unwanted division and
COMMENTS AND CONCLUSIONS
Milk? What have we done to it? We've taken a substance that was
intended for the infant of a species, already loaded with fat,
cholesterol and hormones. We've changed its constitution by
genetically engineering it. We've simmered away its goodness through
pasteurization. We've re-created its components through
homogenization, a treatment in which fat droplets are shattered into
droplets one-tenth their original size and suspended in solution.
FDA now has information indicating that data was manipulated and
withheld from peer review. In addition, new information has surfaced
indicating that the product which was approved for use after many
years of testing is not the same product that is now being used.
Most critically important are the facts presented in the previous two
years of research which indicate that IGF in milk is absorbed intact
and exerts proliferative growth effects.
Armed with the knowledge that virtually all humans have tumors
waiting to proliferate, and milk hormones (IGFs) cause proliferation
of cancer, and that treatment of cows with recombinant bovine growth
hormones causes an increase in IGF levels in milk, it is now time for
science, industry and FDA to re-investigate and re-evaluate this
It is also appropriate that FDA immediately place a moratorium on the
use of rBST until appropriate testing can be completed.
"Isolation of Escherichia coli synthesized recombinant eukaryotic
proteins that contain epsilon-N-acetyllysine."
Violand-BN; Schlittler-MR; Lawson-CQ; Kane-JF; Siegel-NR;
Smith-CE; Kolodziej-EW; Duffin-KL
Animal Sciences Division, Monsanto Corporation, St. Louis,
Protein-Sci. 1994 Jul: 3(7): 1089-97
"Bovine Growth hormone: Human Food Safety Evaluation"
Science, 24 August, 1990, Volume 249, pp. 875-884
"Altered body composition and increased frequency of diverse
malignancies in insulin-like Growth factor-II transgenic mice."
Rogler-CE; Yang-D; Rossetti-L; Donohoe-J; Alt-E; Chang-CJ;
Rosenfeld-R; Neely-R; Hintz-R
Marion Bessin Liver Research Center, Albert Einstein College of
Medicine, Bronx, New York 10461
J-Biol-Chem. 1994 May 13; 269 (19)
"Food safety and Pharmacokinetic studies which support a zero
(0) meat and milk withdrawel time for use of sometribove in
Hammond-BG; Collier-RJ; Miller-MA; McGrath-M; Hartzell-DL;
Monsanto Agricultural Company, Animal Sciences Division, 800 N.
Lindbergh Boulevard, St. Louis, MO 63167
Pharmacokinetics of Veterinary Drugs, 11-12 October 1989
"Regulation of endometrial cancer cell growth by insulin-like growth
factors and the luteinizing hormone-releasing hormone antagonist
Keinman-D; Roberts-CT Jr.; LeRoith-D; Schally-AV; Levy-J; Sharoni-Y
Clinical Biochemistry Department, Faculty of Health Sciences,
Ben-Gurion University of the Negev, Soroka Medical Center of Kupat
Holim, Beer-Sheva, Israel.
Regul-Pept. 1993 Oct 20; 48(1-2) 91-8
"Expression of insulin-like Growth factor II (IGF-II) in human
hepatocellular carcinomas: an immunohistochemical study."
D'Errico-A; Grigoni-WF; Fiorentino-M; Baccarini-P; Lamas-E;
De-Mitri-S; Gozzetti-G; Mancini-AM; Brechot-C Institute of
Pathological Anatomy, University of Bologna, Italy.
Pathol-Int. 1994 Feb; 44(2): 131-7
"Insulin-like Growth factor-I receptor increases in aortic
endothelial cells from diabetic rats."
Kwok-CF: Ho-LT; Jap-TS
Department of Medicine, Veterans General Hospital-Taipei,
Republic of China.
Metabolism. 1993 Nov; 42(11): 1381-5
"Growth factors interact with estradiol and gonadotropins in the
regulation of ovarian cancer cell growth and growth
Wimalasena-J; Meehan-D; Dostal-R; Foster-JS; Cameron-M; Smith-M
Department of Obstetrics/Gynecology, Graduate School of
Medicine, University of Tennessee Medical Center, Knoxville,
Oncol-Res. 1993; 5(8): 325-37
"Effects Of insulin-like arowth factors (IGFs) and IGF receptor
antibodies on the proliferation of human breast cancer cells."
De-Leon-DD; Wilson-DM; Powers-M; Rosenfeld-RG
Department of Pediatric Endocrinology, Stanford University
Medical School, California 94305
Growth Factors. 1992; 6(4): 327-36
"IGF receptor function and regulation in autocrine human
neuroblastoma cell Growth."
Martin-DM; Singleton-JR; Meghani-MA; Feldman-EL
Department of Neurology, University of Michigan, Ann Arbor
Regul. Pept. 1993 Oct 20; 48(1-2): 225-32
"Growth regulation of human alioblastoma T98G cells by
insulin-like Growth factor-I and its receptor."
Ambrose-D; Resnicoff-M; Coppola-D; Sell-C; Miura-M; Rubin-R;
Department of Pathology, Jefferson Medical College,
Philadelphia, Pennsylvania 19107
J-Cell-Physiol. 1994 Apr; 159(1): 92-100
"Insulin-like growth factor II mRNA, peptides, and receptors in a
thoracopulmonary malignant small round cell tumor."
Neilsen-FC; Orskow-C; Haselbacher-G; Ramlau-J; Rehfield-JF;
Kepartment of Clinical Biochemistry, Rigshospitalet,
Cancer. 1994 Feb 15; 73(4): 1312-9
"Dominant negative inhibition of tumorigenesis in vivo by human
insulin-like Growth factor I receptor mutant."
Prager-D; Li-HL; Asa-S; Melmed-S
Department of Medicine, Cedars-Sinai Medical Center
University of California, Los Angeles School of Medicine,
Los Angeles, CA 90048
Proc-Natl-Acad-Sci-U-S-A. 1994 Mar 15; 91(6): 2181-5
"Human osteosarcoma (U-2 OS) cells express both insulin-like
growth factor-I (IGF-I) receptors and insulin-like Growth
factor-II/mannose-6-phosphate (IGF-II/M6P) receptors synthesize
IGF-II: autocrine Growth stimulation by IGF-II via the IGF-I
Raile-K; Hoflich-A; Kessler-U; Yang-Y; Pfuender-M; Blum-WJ
Kolb-H; Schwarz-HP; Kiess-W
Department of Pediatric Endocrinology, Children's Hospital,
University of Munich, Germany.
J-Cell Physiol. 1994 June; 159(3): 531-41
"The insulin-like arowth factor-I/ bindina Protein axis:
physiology, Pathophysiology and therapeutic manipulation."
Academic Department of Medicine, King's College School of
Medicine and Dentistry, London, UK
Eur-J-Clin-Invest. 1993 Sep; 23(9): 503-16
"Trophic action of local intraileal infusion of insulin-like
growth factor-I: polyamine dependence."
Olanrewaju-H; Patel-L; Sledel-ER
Am-J-Physiol. 263:E282-286 (1992)
"Effects of dietary recombinant human insulin-like arowth
factor-I on concentrations of hormones and Growth factors in
the blood of newborn calves."
Baumrucker-CR; Blum JW Department of Dairy and Animal Science,
Pennsylvania State University, University Park, PA 16802
J-Endocrinol. 1994 Jan; 140(1): 15-21
"Hormonal regulation of intestinal adaptation."
Department of Surgery, Royal Children's Hospital, Parkville,
Baillieres-Clin-Endocrinol-Metab. 1994 Jan; 8(1): 165-83
"Effect of Luminal Growth factor Dreservation on intestinal Growth."
Playford-RJ; Woodman-AC; Clark-P; Watanapa-P; Williamson-RC;
Vesey-D; Deprez-PH; Calam-J
The Lancet, 2:843-848, 1993.
"Presence of multiple forms of peptidase inhibitors in rat milk."
Rao-RR; Lam-R; Philipps-AF; Williams-C; Lake-M: Roldovsky-O
Department of Pharmacology, Steele Memorial Children's Research
Center, University of Arizona, Tucson 85724
J-Pediatr-Gastroenterol-Nutr. 1993 Nov; 17(4): 414-20
"Liposomes as a proposed vehicle for the persorption of bovine
Oster-KA; Ross-DJ; Sharnick, S.V.
Proc. Soc. Exper. Bio. & Med., Vol. 163, No. 1 Jan. 1980
"Free Insulin-like Growth factors (IGF-I and IGF-II) in human
Frystyk-J; Skjaerbaek-C; Dinesen-B; Orskov-H
Institute of Experimental Clinical Research, Aarhus University
FEBS-Lett. 1994 July 11; 348(2): 185-91
"The augmentation of insulin-like growth factor-I messenger
ribonucleic acid in cultured rat hepatocytes: activation of
Protein kinease-A and -C is necessary, but not sufficient."
Kachra-Z; Yang-CR; Posner-BI
Polypeptide Hormone Laboratory, Royal Victoria Hospital,
Montreal, Quebec, Canada.
Endocrinology. 1994 Feb; 134(2): 702-8
"Insulin-like Growth factors act synergistically with basic
chromaffin cell proliferation."
Department of Clinical Chemistry, Bispebjerg Hospital,
Proc-Natl-Acad-Sci-U-S-A. 1994 Mar 1; 91(5): 1771-5
"Lactogenic hormones and extracellular matrix regulate
expression of IGF-I linked to MMTV-LTR in mammary erithelial
Romagnolo-D; Akers-RM; Wong-EA; Boyle-PL; McFadden-TB, ByattJC;
Department of Dairy Science, Virginia Ploytechnic Institute and
State University, Blacksburg, VA 24061-0315.
Mol-Cell-Endocrinol. 1993 Oct; 96(1-2):147-57
"Inhibition of Pancreatic cancer cell Growth in vitro by the
tyrphostin Group of tysrosine kinase inhibitors."
Gillespie-J; Dye-JF; Schachter-M; Guillou-PJ
Academic Surgical Unit, St. Mary's Hospital Medical School,
Imperial College of Science, Technology and Medicine, London,
Br.-J-Cancer. 1993 Dec; 68(6): 1122-6
"Identification of insulin-like Growth factor (IGF) and Glucose
transporters and -3 mRNA in CNS tumors."
Glick-RP; Unterman-TG; Lacson-R
Department of Neurosurgery, University of Illinois at Chicago,
Cook County Hospital, 60612
Regul-Pept. 1993 Oct 20: 48(1-2): 251-6
"Alterations in serum levels of insulin-like Growth factors and
insulin-like growth-factor-binding proteins in patients with
Atiq-F; Garrouste-F; Remacle-Bonnet-M; Sastre-B; Pommier-G
Laboratoire d'Immunologie, Faculte de Medecine, Marseille, France.
Int-J-Cancer. 1994 May 15; 57(4): 491-7
"Increased activity of insulin-like Growth factor-binding
protein in human thyroid papillary cancer tissue."
Yashiro-T; Arai-M; Shizume-R; Obara-T; Murakami-H; Hizuka-N;
Emoto-N; Miyakawa-M; Ito-R; Tsushima-T
Department of Surgery, Tsukuba University, Ibaraki, Japan.
Jpn-J-Cancer-Res. 1994 Jan; 85(1): 46-52
"Immunological effects of insulin-like arowth factor-I(IGF-I)
enhancement of immunoglobulin synthesis."
Robbins-K; McCabe-S; Scheiner-T; Strasser-J; Clark-R; Jardie-P
Department of Immunology, Genentech, Inc., South San Francisco,
Clin-Exp-Immunol. 1994 Feb; 95(2): 337-42
Insulin-like growth factor II messenger ribonucleic acid
expression in Wilms tumor, nephrogenic rest, and kidney.
Yun-K; Molenaar-AJ; Fielder-AM; Mark-AJ; Eccles-MR; Becroft-DM;
Department of Pathology, University of Otago Medical School,
Dunedin, New Zealand.
Lab-Invest. 1993 Nov; 69(5): 603-15
"Specific expression of insulin-like Growth factor-II in
rhabdomyosarcoma tumor cells."
Minniti-CP; Tsokos-M; Newton-WA; Helman-LJ
Pediatic Branch, National Cancer Institute, National Institutes
of Health, Bethesda, Maryland 20892.
Am-J-Clin-Pathol. 1994 Feb; 101(2): 198-203
"Human osteosarcoma cell lines are dependent on insulin-like
Growth factor I for in vitro Growth."
Kappel-CC; Velez-Yanguas-MC; Hirschfield-S; Helman-LJ
Molecular Oncology Section, National Cancer Institute,
Bethesda, Maryland 20892.
Cancer-Res. 1994 May 15; 54(10): 2803-7
"Growth factors, receptors and breast cancers."
J. Natl. Inst. Health, Res. 3:59-62 (1991)
IGF-I and related growth factors are critically involved in
aberrant growth of human breast cancer cells.
"Processing of insulin-like Growth factor-II (IGF-II) by human
breast cancer cells."
Lee-AV: Darbre-P; Ring-RJ Imperial Cancer Research Fund,
Breast Biology Group, School of Biological Sciences,
University of Surry, Guildford, UK.
Mol-Cell-Endocrinol. Mar; 99(2): 211-20
"Insulin-like Growth factor-binding Protein enhancement of
insulin-like Growth factor-I (IGF-I)-mediated DNA synthesis and
IGF-I binding in a human breast carcinoma cell line."
Chen-JC; Shao-ZM; Sheikh-MS; Hussain-A; LeRoth-D; Roberts-C
Department of Medicine, University of Maryland School of Medicine,
Baltimore, MD 21201
J-Cell-Physiol. 1994 Jan; 158(1): 69-78
"Recombinant insulin-like Growth factor binding protein-1
inhibits IGF-I serum, and estrogen-dependent Growth of MCF-7
human breast cancer cells."
Figueroa-JA; Sharma-J; Jackson-JG; McDermott-MJ; Yee-D;
Hilsenbeck-SG Department of Medicine, University of Texas
Health Science Center, San Antonio, TX 78284-7884
J-Cell-Physiol. 1993 NOV; 157(2): 229-36
"Retinoic acid inhibition of insulin-like growth factor I
stimulation of c-fos mRNA levels in a breast carcinoma cell
Li-XS; Chen-JC; Sheikh-MS; Shao-ZM; Fontana-JA Department
of Medicine, University of Maryland School of Medicine,
Baltimore, Maryland 21201
Exp-Cell-Res. 1994. Mar; 211(1):68-73
"Insulin-like Growth factor-I (IGF-I) and IGF-binding Protein-2 are
increased in cost fluids of eDithelial ovarian cancer."
Krasnick-A; Menczer-J; Pariente-C; Ranety-H
Institute of Endocrinology, Chaim Sheba Medical Center, Tel-
J-Clin-Endocrinol-Metab. 1994 Feb; 78(2)
"Acute effects of Growth factors on T-47D breast cancer cell
Cancer Biology Division, Garvan Institute for Medical Research,
St. Vincent's Hospital, Darlinghurst, NSW, Australia.
Eur-J-Cancer. 1993; 29A (16) 2273-9
"New Ability to Find Earliest Cancers: A Mixed Blessing?"
New York Times, Science Section. Nov. 8, 1994, Page 1.
The rBST product Monsanto originally tested contained
epsilon-N-acetyllysine instead of lysine as described in the article.
According to the reference cited, Monsanto now filters out this amino
acid (which is normally found in bacteria).
2. Why cut out section on increases in IGF-I in milk from cows
treated with rBST?
Since this paper was being presented to the FDA and the FDA had
already agreed that milk from cows treated with rBST increases the
IGF-I content, Mr. Cohen did not want to get into a debate about what
was already agreed to.
The amount of the increase in IGF-I is very difficult to determine
from the studies available. Apparently, there is no standard assay
being used, but 5 different assays have been used with differing
results. The Juskevich & Guyer paper cites studies which show
varying changes in IGF-I levels from 0 increase to 70% increase up to
300% increase depending upon the assay.
In addition to problems with a lack of a standard assay, experiments
on a small number of animals are not worth much because the IGF-I
levels in milk can change from week to week. What is really needed
is to measure milk trucks using a standard assay.
Monsanto did this when they tested 100 truck-loads of milk from
untreated cows and put the IGF-I level at 4,320 ng/l. In a
measurement of a small number of rBST-treated cows, the IGF-I level
in milk was listed at 35,000 ng/l. However, it is not fair to equate
the two measurements as was pointed out to Mr. Cohen. In Eli Lilly's
application for approval of their rBST-like product, they state that
the IGF-I level in rBST-treated cow milk should not increase above
All parties agree that there will be a significant increase in IGF-I
levels, but there have not been any large-scale testing done (using a
standardized assay) on both treated and untreated cow milk. The FDA
admits that it does not have the facilities for such testing. Mr.
Cohen is try to push for this testing.
3. How is rBST injected?
It is injected intramuscularly. This bypasses the digestive system
so that it is closer to the subcutaneous injections in lab animals
than the oral administration in lab animals.
4. Why was IGF-I assumed to by destroyed by the digestive system.
IGF-I was tested in "Tween-80" in animals and not in commercial milk
products which protects IGF-I from the digestive system.
5. What is EGF?
Epidermal Growth Factor.
6. What is meant by the discussion on glucagon and GH?
Glucagan and GH are present in cows. This gives us clues as to how
rBGH interacts with glucagan and GH to increase IGF-I levels.
7. What is bFGF?
Bovine Folicle Growth Hormone. I think he said that it is found in
BEGIN ENCLOSURE #2
C Greg Guyer 4/27/94
Division of Chemistry
Center for Drug Evaluation
Food and Drug Administration
Rockville, MD 20857
Dear Dr. Guyer:
On May 3rd, we will invalidate the SCIENCE article which you
co-authored with Dr. Juskevich. This will be done before legal
counsel of the City of New York.
I invite you and the Monsanto people, please also bring Mr. Mike
Taylor (the former Monsanto attorney, now Deputy Director FDA) to
come and explain the following:
1. The reasons for the errors between your Ann. Rich. Vet. article
and the SCIENCE article. Please bring a copy of the original
notebook. There are four differences.
2. Why in the summary of your paper statistically significant oral
effects were not mentioned but noted as significant in the Table 5
3. Why no teratogenic [fetal development hazards] data were reported
4. Why no long term exposure data and two year feeding studies were
done on zinc rBGH and rBGH milk, and why the liver effects cited by
Groenewegen brom rBGH milk fed 90 days were ignored (J. Nutrition
5. Why IGF-I was tested only about two weeks when it showed a
statistically significant oral effect during this period of exposure
in some tests.
6. As a policy I invite the Policy Director, Mr. Taylor, to explain
to the public how short term tests are being used to clear chemicals
for long term exposure. Please explain how epidemiology can be
replaced by short term tests. Also explain how we can go from 30
rats to 240 million people using a 90 days test.
7. Please ask Commissioner Kessler to give you a note saying to the
people of New York why no quality assurance test is in the public
domain as for antibiotics imported and so forth.
We look forward to hearing your explanations and also to see the
actual data which were used in the Ann. Rech. Vet. article.
[signed Dr. William C. von Meyer]
Invalidation of Scientific Publication(s) Ann. Rech. Vet. 21,
Suppl. 1, 107s, 1990 and SCIENCE 249, 875, 1990 by Hammond and
Juskevich et. al, respectively, as Documentation for Determination of
Safety of Bovine Growth Hormone Derived Milk and Components of the
Whereas, documents in health research concerning the safety of
materials to large number of consumers must be accurate and precise;
Whereas, large numbers of people are contacted by milk and milk
process products over a life span, and
Whereas, Monsanto Corporation of St. Louis and others propose to
change the process for the manufacture of milk using new h ormone
chemicals, signified as rBGH and rBST from recombinant genetic
processes involving fermentation; and
Whereas, data have been submitted to the F.D.A. on the safety of the
milk and the process and its components, and
Whereas, the data as published show errors and clever deviations from
standard and well established safety practice which would be detected
only by an experienced scientist as given in Attachment 1, and
Whereas, the editor of the publication SCIENCE has shown a bias which
is not permitted in strict science data reviews (Attachment 2) such
that this bias may permit the propagation of errors and
Whereas, data concerning the residual action and occurrence of forms
of IGF-I (insulin-like growth factor -I, a material not well
understood as to its actions) may involved the biochemistry and
development of or enhancement of cancer cell growth, and
Whereas, several experiments show an increase in IGF-I in raw rBGH
milk such that long term feeding tests are mandatory, and
Whereas, a report of off-grad rBGH has leaked to the public as
reported in letters to Dr. Kessler and Ms. Browner (E.P.A.) and the
City Council of New York, and we lack a public quality control
methodology for rBGH, a subject omitted in the SCIENCE paper;
Now, therefore, the SCIENCE and Ann. Rech. Veg. 21, suppl 1 107s
documents defined in the title above are declared invalid as careful
reviews of the health and safety data concerning rBGH milk as
provided in Attachment 1.
Dr. William C. von Meyer 5/1/94
C.E.O., Member N.Y. Academy of Science and
Am. Association of Adv. of Science
The figures in Table 4. of SCIENCE 249, 875, 1990, derived from the
same animals as reported in an article in Ann. Rec. Vet. 21, suppl.
1, 107s lack numerical agreement.
All publications of the health review of rBGH milk lack any long term
or chronic toxicological data in standard animal models; no test
longer than 90 days.
The summary of the SCIENCE article indicates no oral effects were
noted while the tables of data reported indicate, by symbols
indicating statistical significance at P.05 or P.01, oral activity
Reproduction and teratogenicity data have not been published in
SCIENCE and critical tests were not conducted, however, reports of
reproductive disturbances in cow have come to the public's attention
and concern (Montpelier Chronicle Nov. 20, 1991 and comments from Mr.
Kurtz, Lewiston, MN.) In the former report animals receiving a
growth hormone preparation showed retained placenta and skipped
generation teratogenic effects. In the Minnesota report, 19% of the
cows died from stress including hip breakdown after two lactations on
rBGH. These kinds of data have been omitted from the reviews and
freedom of information documents issued to date.
A short term oral feeding test in rat of rBGH milk showed effects on
liver in J. Nutrition 120, 514. The SCIENCE article failed to alert
the public that a 90 day test on 30 rats at a given dose is the
longest test which has been conducted on rBGH milk. Normal tests and
publications regarding chronic safety involve a minimum of two years
exposure and careful observation. In this case the American public
would be asked to accept a product, without a label in many states,
which lacks long term tests, quality control in public labs, and with
only short term test on potenial orally active by-product hormones
The data review of rBGH milk fails to relate for its value in quality
control concerns that other proteins are very toxic at low dosage
and/or orally active such as botulinin, cholera toxin, and even such
vaccines as polio vaccine.
The SCIENCE article assumes digestion of all putative rBGH milk
toxins because they are proteins but fails to cite any well known
stable and orally active proteins.
Long term, or slow diseases, like diabetes and arthritis were not
The Report in SCIENCE fails to related to the public the role of zinc
in the product and process. Of concern is the formation of stable
zinc derivatives which may have unique toxicology and chemistry. A
well known form of zinc protein is the zinc loop protein which can
bind to DNA. Also there is lacking a discussion involving the
problem of women and children contacting raw milk on the farm which
is higher in IGF-I.
Question by Walter McCaffrey, City of New York, to Robert Collier of
Monsanto, "Is Dr. von Meyer's testimony that the longest test on rBGH
milk is 90 days true?"
Reply by Robert Collier, Director Animal Health Research, Monsanto.
(Hearing 194, City of New York, May 3, 1994)
Just prior to this testimony the FDA's publication of the safety data
on rBGH and IGF-I was invalidated by Fairview Industries, Inc. of