What is aspartame? Five surprising facts you never know about this chemical sweetener
(NaturalNews) The controversy surrounding one of the world’s most popular artificial sweeteners, aspartame (NutraSweet, Equal), continues some 30 years after the chemical was rammed through the regulatory process by pharmaceutical interests, despite its well-documented dangers. And yet to this very day, many people are still unaware of the chemical sweetener’s sordid history, not to mention what aspartame is actually made from and how it affects the body and brain.
To many, aspartame is just another FDA-approved sugar alternative that has to be safe, otherwise it wouldn’t be on the market. But the truth about aspartame is much more sinister, including how the chemical sweetener gained market approval http://www.fda.gov. And there’s so much more to the aspartame story that you’ve probably never heard before, thanks to government collusion with powerful drug interests.
More at:
http://www.naturalnews.com/045692_aspartame_chemical_sweetener_surprising_facts.html
From:
http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012203/02P-0317_emc-000202.txt
From: Mark Gold [mgold@shelltown.net]
Sent: Sunday, January 12, 2003 11:15 PM
To: fdadockets@oc.fda.gov
Subject: Docket # 02P-0317 Recall Aspartame as a Neurotoxic Drug: File
#7: Aspartame History
Subject: Docket # 02P-0317
To: FDA Dockets Submittal
From: Mark D. Gold
Aspartame Toxicity Information Center
12 East Side Dr., Suite 2-18
Concord, NH 03301
603-225-2110 begin_of_the_skype_highlighting ![]()
603-225-2110 FREE end_of_the_skype_highlighting
Date: January 12, 2002
Please find below Evidence File #7: Aspartame History
Preapproval "Research" & History of Aspartame
---------------------------------------------
Q. I have been told that there American Medical Association's (AMA)
Council on Scientific Affairs reviewed countless preapproval
studies and found that they failed to reveal toxic side-effects.
Is that true?
A. The AMA council simply repeated what was said by a politically
appointed FDA official. Unfortunately, they didn't do any serious
research on the subject.
While the "research" performed by the aspartame industry after
approval is abyssmal, the *preapproval* "research" was *much*
worse. Despite this fact, FDA officials essentially "sold out"
to the manufacturer and approved the junk.
In order to fully understand the disasterous preapproval process,
it is necessary to highlight important events relating to aspartame
in each year since it was invented. This will be done below. It
starts out slowly, but please stick with it past 1976 when the
preapproval experiment horror stories will begin.
-----------
1964
----
The development of new pharmaceuticals was the focus of
research at the international pharmaceutical company, G.D.
Searle and Company (Farber 1989, page 29). A group working
on an ulcer drug was formed including Dr. Robert Mazer,
James Schlatter, Arthur Goldkemp and Imperial Chemical. In
particular, they were looking for an inhibitor of the
gastrointestinal secretory hormone gastrin (Stegink 1984a,
page 3).
1965
----
In 1965, while creating a bioassay, an intermediate chemical
was synthesized -- aspartylphenylalanine-methyl-ester
(aspartame). In December of 1965, while James Schlatter was
recrystalling aspartame from ethanol, the mixture spilled
onto the outside of the flask. Some of the powder got onto
his fingers. Later, when he licked his fingers to pick up a
piece of paper, he noticed a very strong sweet taste. He
realized that the sweet taste might have been the aspartame.
So, believing that the dipeptide aspartame was not likely to
be toxic, he tasted a little bit and discovered its sweet
taste (Stegink 1984a, page 4). The discovery was reported in
1966, but there was no mention of the sweetness (Furia
1972).
1969
----
The investigators first reported the discovery of the
artificial sweetener in the Journal of the American Chemical
Society stating (Mazur 1969):
"We wish to report another accidental discovery of
an organic compound with a profound sucrose (table
sugar) like taste . . . Prelminary tasting showed
this compound to have a potency of 100-200 times
sucrose depending on concentration and on what
other flavors are present and to be devoid of
unpleasant aftertaste."
--------------
In 1969, former Commissioner of the FDA, Dr. Herbert L. Ley
was quoted as follows (Griffin 1974):
"The thing that bugs me is that people think the
Food and Drug Administration (FDA) is protecting
them -- it isn't. What the FDA is doing and what
the public thinks it's doing are as different as
night and day."
1970
----
The discovery of aspartame is reported in the well-known
publication, Science (Cloninger 1970).
--------------
G.D. Searle approached Dr. Harry Waisman, Biochemist,
Professor of Pediatrics, Director of the University of
Wisconsin's Joseph P. Kennedy Jr. Memorial Laboroatory of
Mental Retardation Research and a respected expert in
phenylalanine toxicity, to conduct a study of the effects of
aspartame on primates. The study was initiated on January
15, 1970 and was terminated on or about April 25, 1971. Dr.
Waisman died unexpectedly in March, 1971.
Seven infant monkeys were given aspartame with milk. One
died after 300 days. Five others (out of seven total) had
grad mal seizures. The actual results were hidden from the
FDA when G.D. Searle submitted its initial applications
(Stoddard 1995a, page 6; Merrill 1977; Graves 1984, page
S5506 of Congressional Record 1985a; Gross 1976b, page 333
of US Senate 1976b).
G.D. Searle denied knowledge of or involvement with the
initiation, design or performance of the study. Yet, the
false results were submitted to the FDA like the rest of the
150 G.D. Searle studies (on aspartame and other products),
bearing a Searle Pathology-Toxicology project number. Both
Dr. Waisman and G.D. Searle were responsible for the study
design. A number of false statements were made by G.D.
Searle including that the animals were unavailable for
purchase for autopsy after the termination of the study.
--------------
Neuroscientist and researcher John W. Olney found that oral
intake of glutamate, aspartate and cysteine (in free form --
unbound to protein such as aspartate in aspartame), all excitotoxic
amino acids, cause brain damage in mice (Olney 1970).
--------------
An internal G.D. Searle memo layed out the strategy for
getting aspartame approved (Helling 1970):
At this meeting [with FDA officials], the basic
philospohy of our approach to food and drugs
should be to try to get them to say "Yes," to rank
the things that we are going to ask for so we are
putting first those questions we would like to get
a "yes" to, even if we have to throw some in that
have no significance to us, other than putting
them in a yes saying habit.
We must create affirmative atmosphere in our
dealing with them. It would help if we can get
them or get their people involved to do us any
such favors. This would also help bring them into
subconscious spirit of participation.
--------------
The FDA banned the sweetener cyclamate. Robert Scheuplein,
who was the acting Director of FDA's Toxicological Services
Center for Food Safety and Applied Nutrition was quoted as
saying "the decision was more a matter of politics than
science." (Stoddard 1995a, page 7)
1971
----
Ann Reynolds, a researcher who was hired by G.D. Searle and
who has done research for the Glutamate (MSG) Association,
confirmed aspartame's neurotoxicity in infant mice (Reynolds
1971).
--------------
Dr. John W. Olney informed G.D. Searle that aspartic acid
caused holes in the brains of mice. G.D. Searle did not
inform the FDA of this study until after aspartame's
approval. None of the tests submitted by G.D. Searle to the
FDA contradicted these findings (Olney 1970, Gordon 1987,
page 493 of US Senate 1987).
1972
----
FDA Toxicologist Dr. Adrian Gross came upon some
irregularities in the submitted tests of the G.D. Searle
drug Flagyl. G.D. Searle did not respond for another two
years. Their response raised serious questions about the
validity of their tests (Gross 1975, page 35; Schmidt 1976b,
page 6).
1973
----
On March 5, 1973, G.D. Searle's petition to the FDA for
approval to market aspartame as a sweetening agent was
published in the Federal Register (1973).
--------------
On March 21, 1973 the MBR report was submitted to G.D.
Searle.
Background
In August of 1970, G.D. Searle conducted two 78-
week toxicity studies on rats for what was to
become a best-selling heart medication, Aldactone.
One study was conducted at G.D. Searle and one at
Hazelton Laboratories. In March 1972, the rats for
autopsied and the pathology slides were analyzed.
For confirmation of the results, G.D. Searle sent
the slides to Biological Research, Ltd. where
board certified pathologist, Dr. Jacqueline Mauro
examined the data. She discovered that the drug
appeared to induce tumors in the liver, testes,
and thyroid of the rats. The report submitted to
G.D. Searle by Dr. Mauro was known as the MBR
Report.
These statistically significant findings were confirmed
by G.D. Searle's Mathematics-Statistics Departement.
Instead of submitting these alarming findings to the
FDA, G.D. Searle contracted with another pathologist,
Dr. Donald A. Willigan. He was given 1,000 slides to
examine. The Willigan Report was more to G.D. Searle's
liking because it revealed a statistically significant
increase in thyroid and testes tumors, but not in liver
tumors. Liver tumors are of much more concern to the
FDA. The Willigan Report was immediately submitted to
the FDA. G.D. Searle did not disclose the MBR Report to
the FDA until August 18, 1975, 27 months after it had
been given to G.D. Searle (Schmidt 1976b, page 14,
Merrill 1977, page S10828-S10831).
At first, G.D. Searle claimed that they did not submit the
MBR Report to the FDA because of an "oversight." Later, they
claimed that Dr. Mauro's MBR report was not submitted
because they did not like the terminology Dr. Mauro used in
evaluating the thyroid slides. They claimed that her
inaccurate terminology in this case showed that Dr. Mauro
was unreliable as a pathologist. Yet, G.D. Searle never
notified Dr. Mauro of any questions and on June 1, 1973,
they wrote to MBR and stated that the report "looks just
fine" (Merrill 1977).
--------------
The FDA Commissioner from 1972 to 1976, Alexander Schmidt,
M.D. felt that "Superficially, it seemed like, if there
would ever be a safe kind of product, that would be it. The
idea that two naturally-occurring amino acids could harm
someone in relatively small amounts...." (Mullarkey 1992,
page 15)
--------------
In an FDA memorandum dated September 12, 1973, Martha M.
Freeman, M.D. of the FDA Division of Metabolic and Endocrine
Drug Products addressed the adequecy of the information
submited by G.D. Searle in their petition to approve
aspartame (Freeman 1973):
"Although it was stated that studies were also
performed with diketopiperazine [DKP] an impurity
which results from acid hydrolysis of Aspartame,
no data are provided on this product."
Commenting on one particular single dose study:
"It is not feasible to extrapolate results of such
single dose testing to the likely condition of use
of Aspartame as an artificial sweetener."
It is important to note that Dr. Freeman pointed out the
inadequency of single-dose tests of aspartame as early as
1973. Since then, the NutraSweet Company has flooded the
scientific community with single-dose studies.
"Chemistry - No information is provided other than
formulae for Aspartame and its diketo-piperazine."
"Pharmacology - Reference is made to 2 year rat
studies, but no data are provided on acute or
chronic toxicity."
"Clinical - No protocols nor curriculum vitae
information are provided for the 10 completed
clinical studies. Results are reported in
narrative summary form, and tabulations of mean
average values only. No information is given as to
the identity of the reporting labs, methodology
(except rarely), or normal values. (Reported units
for several parameters cannot be verified at this
time.)
"No pharmacokinetic data are provided on
absorption, excretion, metabolism, half-life; nor
bioaviliability of capsule vs. food-additive
administration."
Dr. Freeman concludes:
"1. The administration of Aspartame, as reported
in these studies at high dosage levels for
prolonged periods, constitutes clinical
investigational use of a new drug substance."
"2. The information submitted for our review is
inadequate to permit a scientific evaluation
of clinical safety."
She went on to recommend that marketing of aspartame be
contingent upon proven clinical safety of aspartame. The FDA
Bureau of Foods rejected Dr. Freeman's recommendation
(Graves 1984, page S5498 of Congressional Record 1985a).
--------------
Construction of a large aspartame manufacturing plant in
Augusta, Georgia was halted. It was thought that aspartame's
uncertain regulatory future was the main reason for the
stopping of construction (Farber 1989, page 47). In the 1973
G.D. Searle Annual Report, an executive stated that
"commercial quanities of the sweetener will be supplied from
the enlarged facility of Ajinomoto." Ajinomoto is the
inventor and main producer of the food additive MSG.
1974
----
Ninety of the 113 aspartame studies which were submitted by
G.D. Searle to the FDA were conducted in the early to mid-
1970's. All of the tests that were described by the FDA as
"pivotal" were conducted during this time. Eighty percent of
these tests were conducted by G.D. Searle or by their major
contractor, Hazleton Laboratories, Inc. (Graves 1984, page
S5497 of Congressional Record 1985a).
--------------
Dr. J. Richard Crout, the acting director of the FDA Bureau
of Drugs stated that "The information submitted for our
review was limited to narrative clinical summaries and
tabulated mean values of laboratory studies. No protocols,
manufacturing controls infromation or preclinical data were
provided. Such deficiencies in each area of required
information precluded a scientific evaluation of the
clinical safety of this product...." (Mullarkey 1992, page
23)
--------------
Dr. John Olney and Consumer Interest attorney, James Turner,
Esq. met with G.D. Searle to discuss the results of Olney's
experiments. G.D. Searle representatives claim that Olney's
data raises no health concerns (Stoddard 1995a, page 7).
--------------
The FDA approved aspartame for limited use on July 26, 1974.
The allowable uses included free-flowing sugar substitute,
tablets for sweetening hot beverages, cereals, gum, and dry
bases (Farber 1989, Federal Register 1974). It was not
approved for baking goods, cooking, or carbonated beverages.
This approval came despite the fact that FDA scientists
found serious deficiencies in all of the 13 tests related to
genetic damage which were submitted by G.D. Searle.
--------------
In August 1974, before aspartame could go on the market, Dr.
John Olney, James Turner, and Label Inc. (Legal Action for
Buyers' Education and Labeling) filed a formal objection
stating that they believe aspartame could cause brain
damage. They were particularly worried about aspartame's
effects on children (Graves 1984, page S5498 of
Congressional Record 1985a; Federal Register 1975, Olney
1987, page 3).
--------------
G.D. Searle's responses to queries about the testing of
their drug Flagyl, serious and unexpected side effects from
other drugs they developed, and information from Dr. John
Olney's studies started a controversy within the FDA as to
the quality and validity of G.D. Searle's test of aspartame
and pharmaceuticals (Graves 1984, page S5498 of
Congressional Record 1985a).
1975
----
In July 1975, the FDA Commissioner, Dr. Alexander Schmidt
appointed a special Task Force to look at 25 key studies for
the drugs Flagyl, Aldactone, Norpace, and the food additive
aspartame. Eleven of the pivotal studies examined involved
aspartame. All of the studies whether conducted at G.D.
Searle or Hazleton Laboratories were the responsibility of
the Pathology-Toxicology Department at G.D. Searle. (Gross
1987a, page 430 of US Senate 1987). The special Task Force
was headed by Philip Brodsky, FDA's Lead Investigator and
assisted by FDA Toxicologist, Dr. Adrian Gross. The Task
Force was especially interested in "pivotal" tests as
described in an article from Common Cause Magazine by
Florence Graves (Graves 1984, page S5499 of Congressional
Record 1985a):
"Before the task force had completed its
investigation in 1976, Searle had submitted the
vast majority of the more than 100 tests it
ultimately gave the FDA in an effort to get
aspartame approved. These included all tests ever
described as 'pivotal' by the FDA. About half the
pivotal tests were done at Searle; about one-third
were done at Hazleton Laboratories. 'Pivotal'
tests include long-term (two-year) tests such as
those done to determine whether aspartame might
cause cancer. Former FDA commissioner Alexander
Schmidt said in a recent interview that if a
pivotal test is found to be unreliable, it must be
repeated 'Some studies are more important than
others, and they have to be done impeccably,'
Schmidt said."
--------------
G.D. Searle executives admited to "payments to employees of
certain foreign governments to obtain sales of their
products." (Searle 1975)
--------------
On July 10, 1975, Senator Edward Kennedy chaired a hearing
on drug-related research before the Senate Subcommittee on
Health of the Committee on Labor and Public Welfare (US
Senate 1975). Preliminary reports of discrepancies
discovered about G.D. Searle were discussed. The findings of
the FDA Task Force were later presented at further hearings
on January 20, 1976 (US Senate 1976a) and April 8, 1976 (US
Senate 1976b).
--------------
On December 5, 1975, Dr. John Olney and James Turner waived
their right to a hearing at the suggestion of the FDA
General Counsel after the FDA and G.D. Searle agreed to hold
a Public Board Of Inquiry (PBOI) (Federal Register 1975,
page 286, Mullarkey 1994b, page 5-6).
--------------
On December 5, 1975, the FDA put a hold on the approval of
aspartame due to the preliminary findings of the FDA Task
Force. The Public Board of Inquiry is also put on hold
(Mullarkey 1994b, page 5-6; Federal Register 1975). The
evidence of the aspartame pivotal studies were protected
under FDA seal on December 3, 1975 (Sharp 1975).
--------------
G.D. Searle had invested 19.7 million dollars in an
incomplete production facility and 9.2. million dollars in
aspartame inventory. On December 8, 1975, stockholders filed
a class action lawsuit alledging that G.D. Searle had
concealed information from the public regarding the nature
and quality of animal research at G.D. Searle in violation
of the Securities and Exchange Act (Farber 1989, page 48).
1976
----
On January 7, 1976, G.D. Searle submited to the FDA their
proposal for the adoption of "Good Laboratory Practices"
(Buzzard 1976b). G.D. Searle's input was used in FDA's
adoption of Good Laboratory Practices.
--------------
In March 1976, the FDA Task Force completed a 500-page
report with 15,000 pages of exhibits (80-page summary) to
the FDA after completing their investigation (Schmidt 1976c,
page 4 of US Senate 1976b).
--------------
A preliminary statement about the breadth of the
investigation from FDA Toxicologist and Task Force team
member, Dr. Andrian Gross before the US Senate (Gross 1987a,
page 1-2):
"Practices that were noted in connection with any
given such study were quite likely to have been
noted also for other studies that were audited,
and this was a situation which was in no way
unexpected: after all, the set of all such studies
executed by that firm from about 1968 to the mid-
1970's were conducted in essentially the same
facilities, by virtually the same tehnicians,
professional workers and supervisors, and the
nature of such studies does not differ much
whether a food additive or a drug product is being
tested for safety in laboratory animals. It is in
this sense, therefore, that the overall conclusion
summarized at the beginning of the Searle Task
Force Report have relevance to all the studies
audited in 1975 (whether they had references to
aspartame or to any of the six drug products of
Searle's) and, by extension, to the totality of
experimental studies carried out by that firm
around that time -- 1968 to 1975."
A few of the conclusions of the FDA Task Force (Gross 1987a,
page 2-3):
"At the heart of FDA's regulatory process is its
ability to rely upon the integrity of the basic
safety data submitted by sponsors of regulated
products. Our investigation clearly demonstrates
that, in the (case of the) GD Searle Company, we
have no basis for such reliance now."
"We have noted that Searle has not submitted all
the facts of experiments to FDA, retaining unto
itself the unpermitted option of filtering,
interpreting, and not submitting information which
we would consider material to the safety
evaluation of the product . . . Finally, we have
found instances of irrelevant or unproductive
animal research where experiments have been poorly
conceived, carelessly executed, or inaccurately
analyzed or reported."
"Some of our findings suggest an attitude of
disregard for FDA's mission of protection of the
public health by selectively reporting the results
of studies in a manner which allay the concerns of
questions of an FDA reviewer."
"Unreliability in Searle's animal research does
not imply, however, that its animal studies have
provided no useful information on the safety of
its products. Poorly controlled experiments
containing random errors blur the differences
between treated and control animals and increase
the difficulty of discriminating between the two
populations to detect a product induced effect. A
positive finding of toxicity in the test animals
in a poorly controlled study provides a reasonable
lower bound on the true toxicity of the substance.
The agency must be free to conclude that the
results from such a study, while admittedly
imprecise as to incidence or severity of the
untoward effect, cannot be overlooked in arriving
at a decision concerning the toxic potential of
the product."
A few of the relevant findings summarized from various
documents describing the FDA Task Force Report:
a. "Excising masses (tumors) from live animals,
in some cases without histologic examination
of the masses, in others without reporting
them to the FDA." (Schmidt 1976c, page 4 of US
Senate 1976b) Searle's representatives, when
caught and questioned about these actions,
stated that "these masses were in the head and
neck areas and prevented the animals from
feeding." (Buzzard 1976a)
"Failure to report to the FDA all internal
tumors present in the experimental rats, e.g.,
polyps in the uterus, ovary neoplasms as well
as other lesions." (Gross 1987a, page 8).
b. G.D. Searle "stored animal tissues in
formaldehyde for so long that they
deteriorated." (Gordon 1987, page 496 of US
Senate 1987; US Schmidt 1976c, page 25, 27 of
US Senate 1976b)
c. "Instead of performing autopsies on rhesus
monkeys that suffered seizures after being fed
aspartame, the company had financed a new
monkey seizure study with a different
methodology that showed no problems." (Gordon
1987, page 496 of US Senate 1987)
d. "Reporting animals as unavailable for necropsy
when, in fact, records indicate that the
animals were available but Searle choose not
to purchase them." (Schmidt 1976c, page 5 of
US Senate 1976b)
e. Animals which had died were sometimes recorded
as being alive and vica versa. "These include
approximately 20 instances of animals reported
as dead and then reported as having vital
signs normal again at subsequent observation
periods." (Gross 1985, page S10835)
f. "Selecting statistical procedures which used a
total number of animals as the denominator
when only a portion of the animals were
examined, thus reducing the significance of
adverse effects." (Schmidt 1976c, page 4 of US
Senate 1976b)
g. G.D. Searle told the FDA that 12 lots of DKP
were manufacturered and tested in one study,
yet only seven batches were actually made.
(Gross 1985, page S10835)
h. "Significant deviations from the protocols of
several studies were noted which may have
compromised the value of these studies . . .
In at least one study, the Aspartame 52 weeks
monkey study, the protocol was written after
the study had been initiated." (Gross 1985,
page S10835)
i. "It is significant to note that the Searle
employee responsible for reviewing most of the
reproduction studies had only one year of
prior experience, working on population
dynamics of cotton tail rabbits while employed
by Illinois Wildlife Service. In order to
prepare him for this title of 'Senior Research
Assistant in Teratology' (fetal damage) Searle
bought him books to read on the subject and
also sent him to a meeting of the Teratology
Society. This qualified him to submit 18 of
the initial tests to the FDA, in addition to
training an assistant and 2 technicians. He
certainly must have kept them busy because
Searle claimed that 329 teratology
examinations were conducted in just 2 days. He
estimated that he himself examined about 30
fetuses a day, but officials for the Center
for Food and Applied Nutrition could never
determine how that was possible." (Stoddard
1995a, page 9; Graves 1984, page S5500 of
Congressional Record 1985a)
j. "In each study investigated, poor practices,
inaccuracies, and discrepancies were noted in
the antemortem phases which could compromise
the study." (Gross 1985, page S10836 of
Congressional Record 1985b)
k. "Presenting information to FDA in a manner
likely to obscure problems, such as editing
the report of a consulting pathologist . . .
Reporting one pathology report while failing
to submit, or make reference to another
usually more adverse pathology report on the
same slide." (Schmidt 1976c, page 4-5 of US
Senate 1976b)
l. Animals were not removed from the room during
the twice per month exterminator sprayings.
(Gross 1985, page S10836 of Congressional
Record 1985b)
m. Often the substance being tested which was
given to the animals was not analyzed or
tested for homogeneity. "No records were found
to indicate that any treatment mixtures used
in the studies were ever tested or assayed for
pesticide content . . . Running inventory
records for either treatment mixtures or the
test compounds used in treatment mixtures are
not maintained." (Gross 1985, page S10836 of
Congressional Record 1985b)
n. In the Aspartame (DKP) 115 week rat study the
written observations of the pathology report
was changed by the supervising pathologist,
Dr. Rudolph Stejskal even though he was not
physically present during the autopsies and
could not have verified the observations of
the pathologist who did perform the autopsies.
The pathologist who did perform some of the
autopsies had no formal training for such
procedures. (Gross 1985, page S10837 of
Congressional Record 1985b)
o. "Contrary to protocol, slides were not
prepared of this [unusual lesions from the
Aspartame (DKP) study) tissue for microscopic
examinstions . . . ." (Gross 1985, page S10837
of Congressional Record 1985b)
p. "In the Aspartame 46 weeks hamster study,
blood samples reported in the submission to
FDA as 26 week values (for certain specified
animals) were found by our investigators as
being, in fact, values for different animals
which were bled at the 38th week. Many of the
animals for which these values were reported
(to the FDA) were dead at the 38th week."
(Gross 1985, page S10838 of Congressional
Record 1985b)
"It is apparent from the report, that the
Appendix portion contains all the individual
(animal) values of clinical lab data available from
the raw data file. A selected portion of these
values appears to have been used in computing group
means (which were reported to the FDA). It is not
clear what criteria may have been used for
selecting a portion of the data or for deleting the
others in computing the means (reported to the
FDA)." (Gross 1985, page S10838 of Congressional
Record 1985b)
q. "Searle technical personnel failed to adhere
to protocols, make accurate observations, sign
and date records, and accurately administer
the product under test and proper lab
procedures." (Farber 1989, page 109)
r. [There were] "clerical or arithmetic errors
which resulted in reports of fewer tumors."
(Schmidt 1976c, page 27 of US Senate 1976b)
s. [G.D. Searle] "delayed the reporting of
alarming findings." (Schmidt 1976c, page 27 of
US Senate 1976b)
FDA Toxicologist and Task Force member, Dr. Andrian Gross
stated (Wilson 1985):
"They [G.D. Searle] lied and they didn't submit
the real nature of their observations because had
they done that it is more than likely that a great
number of these studies would have been rejected
simply for adequacy. What Searle did, they took
great pains to camouflage these shortcomings of
the study. As I say filter and just present to the
FDA what they wished the FDA to know and they did
other terrible things for instance animals would
develop tumors while they were under study. Well
they would remove these tumors from the animals."
FDA Lead Investigator and Task Force Team Leader, Phillip
Brodsky described the 1975 FDA Task Force members as some of
the most experienced drug investigators. He went on to state
that he had never seen anything as bad as G.D. Searle's
studies (Graves 1984, page S5499 of Congressional Record
1985a).
The report quoted a letter written to G.D. Searle on July
15, 1975 from its consultant in reproduction and teratology,
Dr. Gregory Palmer, in regards to a review of some of G.D.
Searle's repreductive studies submitted to the FDA (Gross
1985, page S10838 of Congressional Record 1985b):
"Even following the track you did, it seems to me
you have only confounded the issue by a series of
studies most of which have severe design
deficiencies or obvious lack of expertise in
animal management. Because of these twin factors,
all the careful and detailed examination of
fetuses, all the writing, summarization and
resummarization is of little avail because of the
shaky foundation."
G.D. Searle officials noted that Dr. Palmer did not look at
all of the teratology studies (Searle 1976b, page 21).
However, there is no credible evidence that would lead a
reasonable person to believe that the studies which were not
presented to Dr. Palmer were much better. In fact, the
evidence shows that it is very likely that all of the
studies were abyssmal.
The FDA Commissioner at the time, Alexander Schmidt stated
(Graves 1984, page S5497 of Congressional Record 1985a):
"[Searle's studies were] incredibly sloppy
science. What we discovered was reprehensible."
Dr. Marvin Legator, professor and director of environmental
toxicology at the University of Texas and the pioneer of
mutagenicity testing at the FDA from 1962 to 1972 was asked
by Common Cause Magazine to review the FDA investigation
results of G.D. Searle's tests (Graves 1984, page S5498 of
Congressional Record 1985a):
"[All tests were] scientifically irresponsible
[and] disgraceful. I'm just shocked that that kind
of sloppy [work] would even be sent to FDA, and
that the FDA administrators accepted it. There is
no reason why these tests couldn't have been
carried out correctly. It's not that we are
talking about some great scientific breakthrough
in methodology."
Senator Edward Kennedy at the April 8, 1976 hearings before
the Senate Subcommittee on Labor and Public Welfare stated
(Kennedy 1976):
"The extensive nature of the almost unbelievable
range of abuses discovered by the FDA on several
major Searle products is profoundly disturbing."
--------------
In January, 1976, G.D. Searle defended their results by
claiming (Searle 1976a, page 5-6):
"In all of the studies at Searle which have been
examined by the FDA in its investigation, the
scope of the material being considered included
seven years of observation, from 1968 to date, in
57 studies involving more than 5,700 animals with
over 228 million observations and calculations."
However, their deliberate misconduct and "lies" (as put by
FDA Investigator, Dr. Adrian Gross) invalidated their
experiments for the following reasons:
1. Many of the problems with the studies included
horrendous experimental designs, questions regarding
dosage given, loss of animal tissue and data, etc.,
etc., which invalidates entire experiments and causes
what they claim to be 4 million observations and
calculations per study (average) to become irrelevant.
2. Only the key aspartame studies were looked at. It is
almost a certainty that the non-key aspartame studies
were equally flawed. Therefore, this would invalidate
the "hundreds of millions" of observations and
calculations made during these studies.
3. The difference between a study showing no statistical
difference and a significant statistical difference is
often only a few observations or calculations.
Therefore, had the myriad of other serious experimental
errors not occurred (as detailed above), the observation
and calculation mistakes in each experiment investigated
would, by themselves, invalidate most of the key
studies.
4. It is highly unlikely that the FDA Investigative teams
found all of the problems with G.D. Searle's studies.
G.D. Searle seemed so intent on covering up their
misconduct, that it is quite likely that they were able
to hide many of the problems from the FDA.
--------------
A series of poorly conceived, flawed studies funded by G.D.
Searle were published in Volume 2 (1976) of the Journal of
Toxicology and Environmental Health. An Associate Editor of
this scientific journal was Robert G. McConnell, the
Director of G.D. Searle's Department of Pathology and
Toxicology (the department responsible for monitoring the
quality of G.D. Searle's pre-approval tests investigated by
the 1975 FDA Task Force). Mr. McConnell's story continues
later in 1977. Another G.D. Searle employee, Carl R.
Mackerer was an editor of the journal. Another editor of the
journal was Thomas R. Tephly, the person responsible for
conducting a series of badly flawed blood methanol and
formate measurements in NutraSweet-funded studies over the
last 15 years.
--------------
In July 1976, the FDA decided to investigate 15 key
aspartame studies submited by G.D. Searle in which the 1975
FDA Task Force discovered problems. Three (3) of the studies
were investigated at the FDA (E5, E77/78, E89) by a 5-member
Task Force headed by FDA veteran Inspector, Jerome Bressler
(Graves 1984, page S5499 of Congressional Record 1985a;
Gordon 1987, page 497 of US Senate 1987; Farber 1989, page
110).
--------------
On August 4, 1976, G.D. Searle representatives met with the
FDA and convinced them to allow G.D. Searle to hire a
private agency, University Associated for Education in
Pathology (UAREP), and pay them $500,000 to "validate" the
other 12 studies (Gordon 1987 page 498 of US Senate 1987)
According the FDA Commissioner during the early 1980s,
Arthur Hull Hayes, the UAREP investigation was to "make sure
that the studies were actually conducted."
As described by Florence Graves (1984, page S5500 of
Congressional Record 1985a):
"The pathologists were specifically told that they
were not to make a judgment about aspartame's
safety or to look at the designs of the tests. Why
did the FDA choose to have pathologists conduct an
investigation when even some FDA officials
acknowledged at the time that UAREP had a limited
task which would only partially shed light on the
validity of Searle's testing? The answer is not
clear.
"Dr. Kenneth Endicott, Director of UAREP, said in
an interview that the FDA had 'reasons to suspect'
that Searle's tests 'were not entirely honest.'
Because the FDA 'had doubts about [Searle's]
veracity,' Edicott said, officials wanted UAREP
'to determine whether the reports were accurate.'
"FDA scientist Dr. Adrian Gross, in a letter to an
FDA official, said, 'speaking as a pathologist, it
seemed questionable that the group could do the
kind of comprehensive investigation that was
required. He pointed in particular to a variety of
issues that needed to be investigated. He said
some of these would involved closely questioning
administrators and lab technicians about their
practices. Since many important issues that should
be investigated 'have nothing to do with
pathology,' he said, only trained FDA
investigators were qualified to do a comprehensive
evaluation of the testing. . . .
"Meanwhile, an interview with Endicott indicates
that Adrian Gross was right: the pathologists
couldn't--and didn't--carry out a comprehensive
review. . . . As former FDA Commissioner Alexander
Schmidt put it in a recent interview, UAREP looked
at the slides to determine whether they had been
misrepresented, but didn't look at the conduct of
the experiments in depth. The 1975 [FDA] task
force investigation looked at the conduct of the
experiments in depth, but did not look at the
slides. . . . Endicott agreed . . . 'We could only
look at what was there--the tissues.'
The findings of this investigation where released in the
Bessler Report in August 1977 (see below).
1977
----
Donald Rumsfeld, who was a former member of the U.S.
Congress and the Chief of Staff in the Gerald Ford
Administration, was hired as G.D. Searle's President.
Attorney James Turner, Esq. alledged that G.D. Searle hired
Rumsfeld to handle the aspartame approval difficulties as a
"legal problem rather than a scientific problem." (Gordon
1987, page 497 of US Senate 1987).
As layed out by Mary Nash Stoddard (Stoddard 1995a, page
11), Rumsfeld hired:
John Robson as Executive Vice President. He was a
former lawyer with Sidley and Austin, Searle's Law
Firm and also served as chairman of the Civil
Aeronautics Board, which was then connect to the
Department of Transportation.
Robert Shapiro as General Counsel. He is now head
of Searle's NutraSweet Division. He had been
Robson's Special Assistant at the Department of
Transportation.
William Greener, Jr., as Chief Spokesman. He was a
former spokesman in the [Gerald] Ford White House.
Donald Rumsfeld is now on the Board of Directors of the
Chicago Tribune which recently wrote a glowing article about
the NutraSweet Company (Millman 1995, Mullarkey 1995).
--------------
On January 10, 1977, FDA Chief Counsel Richard Merrill
recommended to U.S. Attorney Sam Skinner in a 33-page letter
detailing violations of the law that a grand jury be set up
to investigate G.D. Searle. In the letter, Merrill stated
(Merril 1977, page S10827 of Congressional Record 1985b):
"We request that your office convene a Grand Jury
investigation into apparent violations of the
Federal Food, Drug, and Cosmetic Act, 21 U.S..C.
331(e), and the False Reports to the Government
Act, 18 U.S.C. 1001, by G.D. Searle and Company
and three of its responsible officers for their
willful and knowing failure to make reports to the
Food and Drug Administration required by the Act,
21 U.S.C. 355(i), and for conceailing material
facts and making false statements in reports of
animal studies conducted to establish the safety
of the drug Aldactone and the food additive
Aspartame."
All of the G.D. Searle studies were abyssmal as discussed
earlier. However, there were two studies where the
violations of the law appeared to be especially flagrant.
The two studies cited by Merrill were the 52-week toxicity
study on infant monkeys performed by Dr. Waisman which G.D.
Searle withheld key information from the FDA and the 46-week
toxicity study of hamsters where G.D. Searle had taken blood
from healthy animals at the 26th week and claimed that the
tests had actually been performed at the 38th week. Many of
the animals from which G.D. Searle claimed had blood drawn
from were actually dead at the 38th week. See earlier
discussion for references.
--------------
On January 26, 1977, G.D. Searle's law firm, Sidley &
Austin, requested a meeting with U.S. Attorney Samuel
Skinner before a grand jury is convened (Gordon 1987 page
497 of US Senate 1987, Mullarkey 1994b, page 6-7). One
representative of Sidley & Austin at that meeting was Newton
Minow who is currently on the Board of Diretors at the
Chicago Tribune (Gordon 1987, page 497 of US Senate 1987;
Mullarkey 1995).
--------------
On March 8, 1977, in a confidential memo to aides, while he
was supposed to be pushing for fraud indictments against
G.D. Searle, U.S. Attorney Samuel Skinner stated that he had
begun preliminary employment discussions with G.D. Searle's
law firm Sidley & Austin (Gordon 1987, page 497 of US Senate
1987; Mullarkey 1994b, page 7).
--------------
On April 13, 1977, a U.S. Justice Department memo urged U.S.
Attorney Samuel Skinner to proceed with grand jury
investigations of G.D. Searle. The memo points out that the
Statute of limitations on prosecution would run out shortly
(October 10, 1977 for the Waisman monkey study and December
8, 1977 for the hamster study) (Mullarkey 1994b, page 7).
--------------
Samual Skinner withdrew from the G.D. Searle case and
Assistant U.S. Attorney William Conlon was then assigned to
the Grand Jury investigation (Gordon 1987, page 497 of US
Senate 1987).
--------------
On July 1, 1977, U.S. Attorney Samuel Skinner left his job
to work for the G.D. Searle law firm Sidley & Austin. Thomas
Sullivan was appointed as Samuel Skinner's successor (Gordon
1987, page 497 of US Senate 1987).
--------------
Assistant U.S. Attorney William Conlon convened a grand
jury, but he let the Statute of Limitations run out on the
aspartame charges (Gordon 1987, page 497 of US Senate 1987).
Fifteen months later, Conlon accepted a job with the law
firm representing G.D. Searle, Sidley & Austin (Gordon 1987,
page 497 of US Senate 1987).
--------------
Robert McConnell was the Director of G.D. Searle's
Department of Pathology and Toxicology which oversaw most of
the aspartame research. Mr. McConnell was named in Richard
Merrill's letter to U.S. Attorney Samuel Skinner. According
to McConnell's attorney, his client was awarded a $15,000
bonus and asked to take a 3-year sabbatical (for which he
received $60,000/year) because he was a "political
liability." (Gordon 1987, page 496 of US Senate 1987)
--------------
Philip Brodsky, the Lead Investigator for the orginal FDA
Task Force looking into G.D. Searles studies retired. He
stated that his reason for retiring was the disclosure of
the 1975 FDA Task Force findings before the U.S. Congress
(Sen Kennedy hearings in 1976) had become "politicized." As
Gregory Gordon put it in the UPI Investigative article
(Gordon 1987, page 496 of US Senate 1987):
"He said the main witnesses, Searle executives and
top FDA officials uninvolved in the investigation
gave 'the wrong answers to the wrong questions . .
. They didn't even let the experts answer the
questions.'"
--------------
In August 1977, the Bressler Report pertaining to three key
aspartame studies, E5, E77/78 and E89, was released. Some of
the findings from the three studies reviewed by the Bressler-
led FDA Task Force include (Mullarkey 1994b, page 11, 48;
Farber 1989, page 110-112; Verrett 1987, page 385 of US Senate
1987):
a. In one study, 98 of the 196 animals died but were not
autopsied until as much as one year later. Because of
the delay, much of the animal tissue could not be used
and at least 20 animals had to be excluded from
postmortem examinations.
b. The original pathology sheets and the pathology sheets
submitted to the FDA showed differences for 30 animals.
c. One animal was reported alive at week 88, dead from week
92 through week 104, alive at week 108, and finally dead
at week 112.
d. An outbreak of an infectious disease was not reported to
the FDA.
e. Tissue from some animals were noted to be unavailable
for analysis on the pathology sheets, yet results from
an analysis of this "unavailable" tissue was submitted
to the FDA.
f. There was evidence that the diet mix was not homogeneous
allowing the animals to eat around the test substance.
This evidence included a picture and statements by a lab
technician.
g. Fifteen fetuses from animals in one experiment were
missing.
h. Sections from the animals were too thick for
examination.
i. There was no documentation on the age or source of the
test animals.
j. There was no protocol until one of the studies was well
underway.
k. Animals were not permanently tagged to prevent mixups.
l. Some laboratory methods were changed during the study,
but not documented.
A G.D. Searle pathologist referring to the DKP study was
quoted by investigators as saying (Graves 1984, page S5500
of Congressional Record 1985a):
"You should have seen things when this study was
run -- there were five studies being run at one
time -- things were a mess!"
The leader of the Task Force, Jerome Bressler, was quoted as
saying (Gordon 1987, page 497 of US Senate 1987):
"The question you have got to ask yourself is:
Because of the importance of this study, why
wasn't greater care taken? The study is highly
questionable because of our findings. Why didn't
Searle, with their scientists, closely evaluate
this, knowing fully well that the whole society,
from the youngest to the elderly, from the sick to
the unsick . . . will have access to this
product."
--------------
Immediately after the Bressler Report was released, H.R.
Roberts, Director of the FDA's Bureau of Foods created a 5-
person task force to review the Bressler Report. The review
was done by a team at the Center for Food Safety and Applied
Nutrition (CFSAN report). H.R. Roberts would leave the FDA
to become a vice president of the National Soft Drink
Association in 1978. FDA Toxicologist, Jacqueline Verrett
was appointed the Senior Scientist of the Bureau of Foods
Task Force.
On September 28, 1977, H.R. Roberts, Director of the FDA's
Bureau of Foods received a report from a Bureau of Foods
Task Force which claimed that G.D. Searle's studies they
reviewed appeared to be authentic (meaning that they were
actually conducted) (Mullarkey 1994b, page 8).
For each of the major discrpancies found by the Bressler-led
Task Force -- those listed above and many others -- there
was a comment in the FDA Bureau of Foods Report minimizing
the problem. It seemed that no matter how serious the
mistakes were, the FDA Bureau of Foods was determined to
accept the studies by G.D. Searle.
The experimental errors as described above were so bad that
it proved difficult to minimize all of the major errors in
these key studies. In some cases, the best that the CFSAN
could do was to say that "The Task Force could find no
evidence that this was a deliberate attempt to influence the
study." or "It could not be determined if the results would
have been altered...." (Farber 1989, page 111, GAO 1987,
Appendix IV).
The Senior Scientist of the FDA Bureau of Foods Task Force,
Jacqueline Verrett had left the FDA when she openly
discussed the Task Force with UPI Investigative Reporter,
Gregory Gordon (Gordon 1987, page 497 of US Senate 1987):
"Jacqueline Verrett, the senior scientist on the
review team, said members were barred from stating
opinions about the research quality. 'It seemed
pretty obvious that somewhere along that line they
(bureau officials) were working up to a
whitewash,' she said. 'I seriously thought of just
walking off of that task force.' Verrett, now a
private consultant, said that she and other
members wanted to 'just come out and say that this
whole experiment was a disaster and should be
disregarded.'
In her testimony before the U.S. Senate, Dr. Verrett stated
the following (Verrett 1987):
"This authentication was hence intended to verify
that the submitted data had not been altered;
that it reflected the actual outcome of the study,
and that it did not change substantially,
particularly in a statistical sense, the various
parameters from which the conclusion of safety had
been derived.
"Our analysis of the data in this manner revealed
that in these three studies, there were really no
substantial changes that resulted, although in
numerous instances, a definitive answer could not
be arrived at because of the basic inadequacies
and improper procedures used in the execution of
these studies.
"I would like to emphasize the point that we were
specifically instructed not to be concerned with,
or to comment upon, the overall validity of the
study. This was to be done in a subsequent review,
carried out at a higher level.
. . . .
"It would appear that the safety of aspartame and
its breakdown products has still not been
satisfactorily determined, since many of the flaws
cited in these three studies were also present in
all of the other studies submitted by Searle.
. . . .
"Well, they told us in no uncertain terms that we
were not to comment on the validity of it. And I
hoped, although having been there at that point
for 19 years, I should have known better, that
there really would be an objective evaluation of
this beyond the evaluation that we did.
"I do not feel that that was done, based on what I
have read in the GAO report that I have looked at
and so forth. They definately did not objectively
evaluate these studies, and I really think it
should have been thrown out from day one.
"We were looking at a lot of little details and
easy parameters in this study, when the foundation
of the study, the diet and all of these other
things, were worthless. We were talking about the
jockey when we should have been talking about the
horse, that he had weak legs. It is built on a
foundation of sand."
--------------
The FDA general counsel wrote a letter to Consumer Attorney,
James Turner, Esq. responding to Mr. Turner's concern about
the quality and validity of G.D. Searle's experiments. The
FDA stated, "The Public Board of Inquiry on aspartame should
provide a vehicle for definitive resolution, at least for
those studies about which you are most concerned." (Graves
1984, page S5498 of Congressional Record 1985a). As will be
discussed later, Dr. John Olney and James Turner, Esq. were
not allowed to have the quality and validity of the G.D.
Searle studies considered at the Public Board of Inquiry.
1978
----
On December 13, 1978, UAREP submited its results of their
analysis of 12 of G.D. Searle's aspartame studies. UAREP
stated in their report that "no discrepancies in any of the
sponsor's reports that were of sufficient magnitude or
nature that would compromise that data originally
submitted." (Farber 1989, page 33) Remember, the Director of
UAREP pointed out in an interview that their pathologists
did not conduct a comprehensive review of the studies, they
only looked at the animal tissues (Graves 1984, page S5500
of Congressional Record 1985a).
As it turns out, UAREP pathologists who examined the test
results were discovered to have missed and withheld negative
findings from the FDA (Gross 1987b, page 2-5). In some
cases, they completely missed cancerous brain tumors when
analyzing the slides. In addition, some of the slides that
were to be examined by UAREP pathologists were missing even
though they where supposed to have been kept under "FDA
seal." (Olney 1987, page 6-7) FDA Toxicologist Adrian Gross
stated that the UAREP review "may well be interpreted as
nothing short of a whitewash." (Farber 1989, page 114).
Given that the UAREP review results was so biased in favor
of G.D. Searle, one wonders why the FDA would allow a
company being investigated for fraud to pay $500,000 and
hire an outside entity to "validate" their studies.
Even though the UAREP report was biased, there were numerous
instances in that report which demonstrated that G.D. Searle
had not submitted even marginally accurate findings to the
FDA of their pre-approval aspartame tests. For example, in
one study, twelve animals actually had cancerous brain
tumors, yet UAREP reported to the FDA that only three
animals had such tumors (Gross 1987b, page 3-4).
1979
----
In March of 1979, the FDA somehow concluded that G.D.
Searle's aspartame studies could be accepted. They decide to
convene the Public Board of Inquiry (PBOI) which was agreed
to by Dr. John Olney and Attorney James Turner more than
four years earlier (Federal Register 1979).
--------------
In April of 1979, the FDA outlined the specific questions
which were to be addressed by the PBOI. The FDA limited the
scope of the PBOI to (Federal Register 1981):
a. Whether the ingestion of aspartame either
alone or together with glutamate poses a risk
of contributing to mental retardation, brain
damage, or undesireable effects on
neuroendocrine regulatory systems.
b. Whether the ingestion of aspartame may induce
brain neoplasms (tumors) in the rat.
c. Based on answer to the above questions.
(i) Should aspartame be allowed for use in
foods, or, instead should approval of
aspartame be withdrawn?
(ii) If aspartame is allowed for use in
foods, i.e., if its approval is not
withdrawn, what conditions of use and
labeling and label statements should be
required, if any?
Dr. John Olney, G.D. Searle, and the FDA's Bureau of Foods
were allowed to nominate scientists for the 3-person PBOI
panel (Farber 1989, page 34, Federal Register 1981, page
38286).
It is important to note that the scope of the review was
very limited in light of all of the various adverse
reactions reported to the FDA. The PBOI also disallowed any
discussion of the validity of the pre-approval experiments
because it accepted the word of certain FDA officials that
these experiments had been "validated." Finally, the PBOI
was told not to consider aspartame in beverages, only in dry
goods.
--------------
In June of 1979, the acting FDA Commissioner, Sherwin
Gardner selected the 3-person Public Board of Inquiry. The
panelists were Peter J. Lampert, M.D., Professor and
Chairman, Department of Pathology, University of California
(San Diego), Vernon R. Young, Ph.D., Professor of
Nutritional Biochemistry, M.I.T., and Walle Nauta, M.D.,
Ph.D., Institute Professor, Department of Psychology and
Brain Science, M.I.T.
Dr. John Olney strongly objected to the Commissioner's
selection of one of the panelists, Dr. Vernon Young, on
grounds of conflict of interest and lack of qualifications
(Olney 1987, page 3). Dr. Young had written nonaspartame-
related articles in collaboration with G.D. Searle
scientists (Brannigan 1983, page 196). In addition, Dr.
Olney stated that the question of aspartic acid's
neurotoxicity should be looked at by a neuropathologist and
that Dr. Young was unqualified since his field was Nutrition
and Metabolism. Dr. Olney's objections were overruled by
acting FDA Commissioner Sherwin Gardner and the panelists
who he objected to was assigned to study the issue of
aspartic acid toxicity.
One of the PBOI members, Dr. Walle Nauta stated (Graves
1984, page S5498 of Congressional Record 1985a):
"It was a shocking story we were told [about
Searle's animal testing] but, there was no way we
could go after it. We had absolutely no way of
knowing who was right. We had to take the FDA's
word."
Dr. Nauta stated that he would have "definately" considered
other tests and factors if he had known that aspartame was
planned for use in soft drinks (Graves 1984, page S5503 of
Congressional Record 1985a).
1980
----
The Public Board Of Inquiry voted unanimously to reject the
use of aspartame until additional studies on aspartame's
potential to cause brain tumors could be done. The PBOI was
particularly concerned about experiment E33/34 where 320
rats received aspartame and a much higher percentage of
animals in the aspartame group developed tumors than in the
control group (Brannigan 1983, page 196). In addition, the
PBOI was concerned about experiment E70 where 80 rats
received aspartame. Both the aspartame group and the control
group had an unusually high number of tumors, leading one to
suspect that both groups were actually given aspartame
(Federal Register 1981).
The PBOI did not believe that aspartic acid presented a
neurotoxic hazard. Yet, Dr. Olney pointed out that (Olney
1987, page 3):
"[Dr. Young had a] lack of qualification" and that
he "based his decision on a consideration of
[aspartic acid] alone without regard to the real
issue, i.e., is it safe to add [aspartic acid] to
the large amounts of [glutamic acid/MSG] that are
already adultering the food supply?"
In addition, the "conservative" safety plasma level of
aspartic acid used by Dr. Young was the level at which half
the animals developed brain damage (Brannigan 1983, page
197). These errors by Dr. Young throw the question of safety
of aspartic acid as part of aspartame into doubt. We will
address this issue in more detail in a later section.
1981
----
On January 21, 1981, the day after Ronald Reagan takes
office as U.S. President, G.D. Searle reapplied for the
approval of aspartame. G.D. Searle submits several new
studies along with their application. It was believed that
Reagan would certainly replace Jere Goyan, the FDA
Comissioner. G.D. Searle president, Donald Rumsfeld's
connections to the Republican party were also thought to
play a part in Searle's decision to reapply for aspartame's
approval on the day after Ronald Reagan was inaugurated
(Gordon 1987, page 499 of US Senate 1987).
--------------
According to a former G.D. Searle salesperson, Patty Wood-
Allott, G.D. Searle president, Donald Rumsfeld told his
salesforce that, if necessary, "he would call in all his
markers and that no matter what, he would see to it that
aspartame would be approved that year." (Gordon 1987, page
499 of US Senate 1987)
--------------
In March of 1981, a 5-member panel of scientists was
established by the FDA Commissioner Jere Goyan to review the
issues raised by the PBOI (Gordon 1987, page 498 of US
Senate 1987; Mullarkey 1994b, page 8).
--------------
In April 1981, Arthur Hull Hayes, Jr. was appointed FDA
Commissioner by Ronald Reagan (Graves 1984, page S5502 of
Congressional Record 1985a).
--------------
On May 18, 1981, three of the scientists in the 5-member
panel sent a letter to the panel lawyer, Joseph Levitt
discussing their concerns about aspartame. Those three
scientists were Satva Dubey (FDA Chief of Statistical
Evaluation Branch), Douglas Park (Staff Science Advisor),
and Robert Condon (Veterinary Medicine). Dubey thought that
the brain tumor data was so "worrisome" in one study that he
could not recommend approval of aspartame (Gordon 1987, page
495 of US Senate 1987). In another study, Dubey said that
key data appeared to have been altered (Gordon 1987, page
499 of US Senate 1987).
In his UPI Investigation, Gregory Gordon went on to describe
the unusual events that followed (Gordon 1987, page 499 of
US Senate 1987):
"[Douglas] Park said that [panel lawyer Joseph]
Levitt hurried the panel to decide the issue.
'They wanted to have the results yesterday,' he
said. 'We really didn't have the time to do the in-
depth review we wanted to do.'
"Park said Levitt met frequently with Hayes and
'was obviously getting the pressure to get a
resolution and a decision made.'
"With three of five scientists on the
commissioner's team opposing approval, it was
decided to bring in a toxicologist for his opinion
on isolated issues [Barry N. Rosloff]. Goyan said
if the decision were his, he never would have
enlarged the team. While the panel did not vote,
it ended up split 3-3.
"Levitt, who normally would have been expected to
draft an options paper spelling out scientific
evidence on key issues, took an unusual tack. He
circulated an approval recommendation and only
backed off when Dubey, Park, and Condon objected,
team members said. Levitt said he was not directed
to draft the approval memo, but did so as a
'tactical' step to break the team's weeks-long
impasse by forcing each scientist to state his
views. 'It worked, didn't it?' said Levitt, who
later was promoted to a post as an executive
assistant to the FDA Commissioner."
--------------
On July 18, 1981 aspartame was approved for use dry foods by
FDA Commissioner Arthur Hull Hayes, Jr. overruling the
Public Board of Inquiry and ignoring the law, Section
409(c)(3) of the Food Drug and Cosmetic Act (21 U.S.C. 348),
which says that a food additive should not be approved if
tests are inconclusive (Federal Register 1981, Farber 1989,
page 38). In an article in Common Cause Magazine, Florence
Graves states that two FDA officials said that Arthur Hull
Hayes, Jr. wanted to push aspartame approval through in
order to signal reforms of the Reagan Administration. The
"reasoning" behind the FDA Commissioner's decision will be
discussed in a later section (Graves 1984, page S5497 of
Congressional Record 1985a).
1982
----
On October 15, 1982, G.D. Searle petitioned the FDA for
approval to use aspartame in soft drinks and children's
vitamins (Gordon 1987, page 499 of US Senate 1987; Farber
1989, page 38)
--------------
On October 1, 1982 an amendment was attached to the Orphan
Drug Act (an act which encourages the development of drugs
for rare diseases) which modified the U.S. Patent law
(Congressional Record 1982). The amendment extended the
patent on only one product -- aspartame -- by 5 years, 10
months and 17 days (Gordon 1987, page 504 of US Senate
1987). The amendment did not mention aspartame or G.D.
Searle by name and there was no debate or discussion on the
amendment.
The amendment was proposed by Senator Howell Heflin, brought
up for a vote by Senator Robert Byrd, and pushed through by
Representative Henry Waxman and Orrin Hatch. G.D. Searle
asked Senator Heflin to sponsor the amendment. Heflin
received $9,000 in campaign donations shortly after this
amendment was approved from G.D. Searle company executives
and their wives. Senator Byrd had received a $1,000 campaign
contribution from the CEO of G.D. Searle before the
amendment was proposed. Representative Waxman received a
$1,500 campaign contribution from the soft drink political
action committee including $500 before the amendment was
proposed. Senator Hatch received $2,500 from the soft drink
political action committee prior to his reelection and
$1,000 each from Daniel Searle, Wesley Dixon (Daniel
Searle's brother-in-law), and William Searle (Gordon 1987,
page 506 of US Senate 1987). Senator Hatch repeatedly
blocked hearings looking into the safety of aspartame
(Gordon 1987, page 506 of US Senate 1987).
It could be argued that the amendment to extend G.D.
Searle's patent of aspartame rectified the lost marketing
time caused by the FDA investigations. However, it was G.D.
Searle's horrendous pre-approval studies which led to the
FDA investigations and the delays. Had they performed the
studies with any competance, aspartame could have been
approved quickly like any other FDA-approved food additive.
(Actually, had the studies been done right, it is likely
that aspartame would never been approved due to serious
adverse reactions.) In addition, the amendment was
applicable to one product and cannot be used similarly for
other products.
--------------
Between 1979 and 1982, four FDA officials who took part in
the aspartame approval process went through the FDA
revolving door and took jobs in industries that are closely
linked with the NutraSweet issue (Gordon 1987, page 498 of
US Senate 1987):
1. Mike Taylor was an FDA lawyer who represented the FDA
Bureau of Foods at the PBOI and was part of the team
that prevented the quality and validity of G.D. Searle's
studies from being considered (Gordon 1987, page 498 of
US Senate 1987).
2. Sherwin Gardner was the Deputy FDA Commissioner in 1979.
In July, 1974, he had signed the initial approval for
aspartame's use in dry foods. (This initial approval was
later block by objections from James Turner, Esq. and
Dr. John Olney.)
In December, 1979, Sherwin Gardner became a Vice
President of Grocery Manufacturers of America, Inc. (GAO
1986). While Mr. Gardner claims that he did not discuss
aspartame is his 4 meetings with the FDA within a year
of leaving that agency or his 20 meetings with the FDA
between 1980 and 1986, the organization he worked for
does deal directly with aspartame products. It is
unlikely that he would have been rewarded with the job
had he called for another delay in approval and proposed
that safety tests be conducted independantly in order to
protect the public.
3. Stuart Pape was the Health and Human Services (HHS)
Chief Counsel for Foods from October 1976 to March 1979.
He served as special assistant to the FDA Commissioner
from March 1979 to December 1979. He participated in
meetings and discussions on aspartame as well as
representing the FDA at the PBOI.
In December 1979, Mr. Pape was given a job by the law
firm of Patton, Boggs, and Blow. This law firm provided
counself to the National Soft Drink Association (NSDA).
Mr. Pape and Howard R. Roberts of the NSDA (who formerly
fought for approval of aspartame at the FDA) met with
the FDA twice in 1983 where aspartame was discussed. In
1983, the NSDA inexplicably withdrew their objection to
aspartame in diet beverage (GAO 1986).
4. Albert Kolbye was the Associate Director of the FDA
Bureau of Foods for toxicology.
1983
----
Acting FDA Commissioner, Mark Novitch approved aspartame for
use in carbonated beverages and carbonated beverage syrup
bases (Federal Register 1983). FDA Commissioner, Arthur Hull
Hayes was out of town the day that the approval was signed,
but he worked closely with Mark Novitch on this issue
(Gordon 1987, page 499 of US Senate 1987). Ignoring the
FDA's own safety standards, they more than doubled the
Acceptable Daily Intake (ADI) of aspartame from 20 mg/kg to
50 mg/kg (Metzenbaum 1985).
--------------
Shortly after the FDA approval for aspartame in carbonated
beverages, FDA Commissioner, Arthur Hull Hayes left the FDA
under charges of improprieties, took a a position as the
Dean of New York Medical Collage and was hired as an a
consultant ($1,000 per day) with G.D. Searle's public
relations firm, Burston Marsteller (Gordon 1987, page 499 of
US Senate 1987).
--------------
On July 8, 1983, Dr. Woodrow Monte, Director of the Science
and Nutrition Laboratory at Arizona State University filed a
petition objecting to the approval of aspartame based on
possible serious adverse effects from the chronic intake of
aspartame. Dr. Monte was especially concerned about the
chronic intake of methanol (Federal Register 1984). Dr.
Monte also filed a petition with the Arizona Department of
Health Services to ban aspartame.
--------------
On July 8, 1983, James Turner, Esq. filed a peition with the
FDA on behalf of himself and Community Nutrition Institute
objecting to the approval of aspartame (Federal Register
1984).
--------------
Dr. Woodrow Monte, at the suggestion of his lawyer, invested
$2,000 in G.D. Searle stock options in order to raise money
for his costly legal battles against aspartame. He ended up
losing $1,224. His purchasing of the "put options" caused
some controversy. Dr. Monte was later accused of conflict-of-
interest by G.D. Searle. Dr. Monte's lawyer had told him
that he "didn't think there was anything wrong" with
purchasing the options. A move that Dr. Monte later called a
mistake. (Gordon 1987, page 508 of US Senate 1987)
--------------
On November 23, 1983, the FDA denied a request to put the
approval on hold "because public interest did not require
it." (Federal Register 1984).
1984
----
On February 17, 1984, the FDA denied Dr. Woodrow Monte and
James Turner the opportunity to hold a safety hearing on
questions raised in their petition (Federal Register 1984).
--------------
G.D. Searle sent a number lobbyists to the State of Arizona
including Andrew Herwitz, Arizona Governor Babbitt's former
Chief of Staff, Charles Pine, a prominent Arizona lobbyist,
Roger Thies, a G.D. Searle lawyer, and David West, a G.D.
Searle official (Gordon 1987, page 507 of US Senate 1987;
Stoddard 1995a, page 17).
--------------
The State of Arizona DHS completed studies showing that
aspartame in carbonated beverages can break down into free
methanol (among other things) in 99oC temperatures. The
amount of methanol which broke down concerned the DHS enough
that a ban of aspartame was discussed (Gordon 1987, page 507
of US Senate 1987).
--------------
Between August 23, 1984 and September 21, 1984, G.D. Searle
officials contributed to the campaign of Arizona House
Majority Leader Burton Barr. The Committee to Reelect Barr
then gave campaign contributions to a number of state
representatives (Don Aldridge, Karen Miills, Jan Breuer) who
all eventually voted of the side of G.D. Searle (Gordon
1987, page 507 of US Senate 1987).
--------------
Dr. Woodrow Monte's petition for a hearing regarding banning
aspartame in Arizona was rejected (Gordon 1987, page 507 of
US Senate 1987).
--------------
6,900,000 pounds of aspartame were consumed in the U.S. in
1984 (USDA 1988).
1985
----
Dr. Richard Wurtman of MIT is quoted as saying that Dr.
Gerald Gaull, a G.D. Searle Vice President, came to his
laboratory and threatened to veto his funding from the
International Life Sciences Institute (ILSI) after Wurtman
quit his job as a G.D. Searle consultant and became a
NutraSweet opponent (Gordon 1987, page 503 of US Senate
1987).
--------------
Dr. Woodrow Monte filed for reconsideration of his petition
for a hearing in Arizona. He was granted a hearing scheduled
for April 1985 (Gordon 1987, page 507 of US Senate 1987).
--------------
In April 1985, in an unusual and secret maneuver, the
Arizona legislature removed the text in a Toxic Waste Bill
and used it to pass a bill which banned the regulation of
FDA-approved food additives (Gordon 1987, page 508 of US
Senate 1987). This bill scuttled the hearing that Dr. Monte
had been promised.
--------------
On May 7, 1985, the U.S. Senate heard testimony relating to
an amendment put forth by Senator Howard Metzenbaum
requiring the quantity of aspartame to be labelled
(Congressional Record 1985a). It is nearly impossible for a
person to determine what quantity of aspartame they are
ingesting unless it is labelled. Senator Orrin Hatch of Utah
led the fight (along with G.D. Searle) against the labelling
ammendment. The ammendment was defeated. Those voting
against the amendment included:
Abdnor, Armstrong, Baucus, Bentsen, Biden, Bingaman, Boren,
Boschwitz, Bradley, Bumpers, Cochran, Cohen, D'Amato,
Danforth, DeConcini, Denton, Dixon, Dole, Domenici,
Durenberger, Evans, Ford, Garn, Goldwater, Gore, Gorton,
Gramm, Gassley, Hatch, Hawkins, Hecht, Heflin, Heinz, Helms,
Hollings, Humphrey, Inouye, Kassebaum, Kasten, Laxalt,
Leahy, Levin, Lugar, Mattingly, McClure, McConnell,
Mitchell, Murkowski, Nickles, Nunn, Packwood, Pressler,
Pryor, Quayle, Riegle, Roth, Rudman, Sasser, Simpson,
Stafford, Stevens, Symms, Thurmond, Tribe, Wallop, Warner,
Wilson, Zorinsky.
Those voting for the amendment included:
Burdick, Byrd, Chafee, Chiles, Cranston, Dodd, Eagleton,
Glenn, Harkin, Hart, Hatfield, Johnston, Kennedy, Kerry,
Lautenberg, Long, Mathias, Matsunaga, Melcher, Metzenbaum,
Moynihan, Pell, Proxmire, Rockefeller, Sarbanes, Simon,
Spector.
--------------
On August 1, 1985, Senator Howard Metzenbaum of Ohio
introduced a bill entitled "Aspartame Safety Act of 1985"
which required quantity labelling of aspartame on food items
and mandated that there be a moratorium on new uses of
aspartame until independent tests could be conducted under
the auspices of the National Institutes of Health
(Metzenbaum 1985). Testimony was submitted for the record.
The bill was submitted to a Senate committee where it died.
--------------
After suffering a $28 million dollar loss in the previous
year, selling off 30 subsidaries, and having a suit filed by
780 women claiming that G.D. Searle's intrauterine device
caused them pelvic inflammatory disease, G.D. Searle sold
out to the chemical company, Monsanto (Gordon 1987, page 509
of US Senate 1987). Monsanto then created the NutraSweet
Company as a subsiderary separate from G.D. Searle.
--------------
14,400,000 pounds of aspartame were consumed in the U.S. in
1985 (USDA 1988).
1986
----
Community Nutrition Institute (CNI) filed suit against the
FDA in District Court claiming that the FDA did not follow
proper procedure in approving aspartame for beverages and
that they should have held a public hearing before giving
final approval (Farber 1989, page 39). After the District
Court dismissed their suit and the D.C. Circuit Court of
Appeals denied their request for a hearing stating that they
failed to "raise any material issues of fact that require
the FDA to grant a hearing," CNI stated:
...where the holding of a public hearing is no
longer a responsible part of the food additive
process, the F.D.A. and the appeals court have
increased the likelihood that unsafe food
additives will reach the market.
--------------
In July 1986, the U.S. General Accounting Office (GAO)
published the results of an investigation of five former
government employees involved in the aspartame approval
process who took jobs linked to the aspartame industry (GAO
1986). While these former employees' actions were not
illegal, it is a good example of how the U.S. Government and
especially the FDA "revolving door" helps certain powerful
companies have near complete control over governmental
actions. Government employees will give industry whatever it
wants (and the public be damned). Then many of these
employees will be rewarded with high-paying industry jobs.
Some of those people will then end up back in government in
order to do more favors for their industry friends -- even
if it means destroying people's lives and health. The inner-
city gangs are not the only place where morally corrupt
individuals operate with near impunity.
--------------
15,700,000 pounds of aspartame were consumed in the U.S. in
1986 (USDA 1988).
1987
----
The United Press reported on October 12, 1987 that more than
10 federal officials involved in the NutraSweet decision
took jobs in the private sector linked to the aspartame
industry (Gordon 1987, page 495 of US Senate 1987).
--------------
On November 3, 1987 a hearing was held in a U.S. Senate
Committee to address the issue of aspartame safety and
labelling (US Senate 1987). Senator Orin Hatch successfully
block any labelling requirements.
--------------
In June 1987, the U.S. General Accounting Office (GAO)
published the results of an investigation which looked into
whether the FDA followed its required approval process (GAO
1987). The report concluded:
"Because FDA followed its required approval
process in approving aspartame and monitors
adverse reactions and ongoing aspartame research,
GAO is making no recommendations."
It is important to note that the author of the report
specifically stated on the first page:
"We did not evaluate the scientific issues raised
concerning the studies used for aspartame's
approval or FDA's resolution of these issues, nor
did we determine aspartame's safety. We do not
have such scientific expertise."
The GAO seemed only interested in whether the FDA took the
legally appropriate steps, not whether or not the FDA's
decisions were based on the facts or made any sense.
- They were not interested in the fact that CFSAN's
evaluation of the Bressler report was a "whitewash" in
the words of the head scientist of the CFSAN team.
- They were not interested in the severe reactions
suffered by many of the animals in the preapproval
studies.
- They were not interested in the countless, major flaws
in the preapproval studies as described earlier.
- They were not interested in the fact that the FDA
Commissioner, who later consulted for the G.D. Searle
Public Relations firm (at $1,000 per day), over-ruled
the Public Board of Inquiry (PBOI) experts and over-
ruled his own chosen scientific experts to approve
aspartame.
- They were not interested that the FDA decided to allow
G.D. Searle to pay UAREP $500,000 to "validate" 15 of
their studies.
They were only interested in whether the legally required
steps were taken. Even with the limited scope of the GAO
investigation, they made numerous factual errors in their
report, some of which are detailed in the letter from fromer
FDA Investigator and Toxicologist Dr. Andrian Gross
presented before the U.S. Senate in 1987 (Gross 1987b, page
11). Dr. Gross concludes:
"Although in their report the GAO expresses the
view that the FDA 'followed its required process
in approving aspartame (for marketing)' I would
sharply disagree with such evaluation. Although
the FDA may have gone through the motions or it
may have given the appearance of such a process
being in place here, the people of this country
expect and require a great deal more from that
agency charged with protecting their public
health:- in addition to mere facade or window-
dressing on the part of the FDA, they require a
thorough and scientifically based evaluation by
the Agency on the safety of the products it
regulates.
"Unfortunately this has clearly not been the case
here. And without this kind of assurance, any such
'process' or dance represents no more than a farce
and a mockery of what is truly required."
--------------
An estimated 17,100,000 pounds of aspartame were consumed in
the U.S. in 1987 (USDA 1988). NutraSweet stopped providing
consumption data to the USDA after 1987. It is much easier
for NutraSweet scientists to create inaccurate aspartame
consumption figures when the total number of pounds sold is
not publically available, or is inaccurate when it is given
out publically.
1988
----
In August 1988, aspartame was approved for use in Brazil
(Monsanto 1990). Thanks to a massive advertising campaign,
at the end of 1990, 150 products were sweetened exclusively
by aspartame.
1990
----
In May 1990, Nutrasweet opened a production facility in Sao
Jose dos Campos, Brazil (Monsanto 1990). There was no diet
foods in Brazil in the 1980s. Unfortunately, part of
NutraSweet's efforts "to build a diet segment from zero" in
Brazil will likely lead to many people in Brazil obsessing
about the weight and appearance which in turn often leads to
eating disorders and other psychological problems. At the
same time, NutraSweet is beginning to dose the population
with their slow poison.
1991
----
NutraSweet joined with its long-time partner, Ajinomoto Co.
Inc. of Japan to begin building an aspartame manufacturing
plant in Gravelines, France (Monsanto 1991).
--------------
The NutraSweet Company began a project to develop a new
artificial sweetener, called "Sweetener 2000" which is said
to be approximately 10,000 times sweeter than sugar. The
chemical composition of this sweetener was not detailed in
Monsanto's Annual Report. NutraSweet's plan is to get this
new sweetener to the market by the end of the decade
(Monsanto 1991).
1992
----
NutraSweet signed agreements with the Coca-Cola Co. and
PepsiCo Inc. "stipulating The NutraSweet Company as their
preferred supplier of aspartame (Monsanto 1992).
--------------
NutraSweet stated that one of their options for increases
sales in the carbonated soft drink market is to prepare
"higher-concentration formulations that use more aspartame"
(Monsanto 1992).
--------------
The FDA approved the NutraSweet Company's application to
market aspartame in bulk form. NutraSweet markets the
product under the name "NutraSweet Spoonful" (Monsanto
1992).
--------------
The patent for aspartame expired on December 14, 1992
opening up the market to other companies such as Holland
Sweetener Company (Monsanto 1992).
1993
----
In mid-1993, NutraSweet and long-time partner, Ajinomoto Co.
of Japan began producing aspartame from the new production
facility in Gravelines, France (Monsanto 1993).
--------------
NutraSweet began a joint venture with Nestle Mexico to bring
aspartame to Mexico (Monsanto 1993).
--------------
NutraSweet began to explore other aspartame marketing
opportunities in Mexico (Monsanto 1993).
1994
----
NutraSweet introduced tabletop aspartame products to Mexico,
Hungary, Uganda, Ecuador, Romania, Uruguay, and Paraguay
(Monsanto 1994).
--------------
Aspartame's net sales outside of the U.S. accounts for 10
percent of all net sales (Monsanto 1994).
--------------
As detailed by investigative journalist Gregory Gordon (Gordon
1996):
"Between the early 1980s and 1994, scientists at the National Institutes
of Environmental Health Sciences (NIEHS) proposed at least four times
that the government's leading program for toxicology research fund such
studies."
"The government scientists said they wanted the National Toxicology
Program to conduct animal studies to resolve questions about the
sweetener's cancer risks."
"After each of these "nominations," NIEHS officials elected not to pursue
the research at the urging of FDA officials, who said they were
satisfied with industry-sponsored research that found no health
risks."
--------------
NutraSweet announced plans to market aspartame tabletop
sweeteners in 1995 throughout Southeast Asia. They plan to
introduce aspartame to India and to test market an aspartame
tabletop sweetener in China during 1995 (Monsanto 1994).
1995
----
In a June 12, 1995 article which appeared in Food Chemical
News, Thomas Wilcox, the FDA epidemiology branch chief was
quoted as saying, "FDA has no further plans to continue to
collect adverse reaction reports or monitor research
periodically done on aspartame." (Food 1995)
--------------
Monsanto/NutraSweet is beginning to test market Equal in
Shanghi, China. It is part of a plan to push their poison on
60 million Chinese in the coastal cities (Millman 1995).
1996
----
Distinguished Neuroscientist research, Dr. John W. Olney, publishes
research showing that aspartame may be a brain tumor agent. He shows
that aspartame caused brain cancer in preapproval research, that a
breakdown product of aspartame has caused mutations in vitro, and
that from 4 to 13 years after approval there was a significant
increase in the conversion of less deadly brain tumors to much more
deadly brain tumors (same types as seen in preapproval research) in
susceptible populations (Olney 1996). Monsanto and the FDA respond
with irrelevant statements regarding the overall brain tumor rate
(NutraSweet 1996).
[Note: Politically/Financially motivated decisions that completely
ignore public health (as seen throughout this document) are fairly
common in the U.S. when it comes to food, drugs, and chemical
"safety."]
References
----------
Brannigan, Vincent, 1983. "The First FDA Board of Inquiry:
The Aspartame Case," IN "Law and Science in
Collaboration," edited by J.D. Nyhart and Milton M.
Carrow, Lexington Books, D.C. Heath and Company,
Lexington, Massachusetts, c1983, page 181-210
Buzzard, James A., 1976a. Testimony of James A. Buzzard,
G.D. Searle, before the U.S. Senate Joint Hearings before
the Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 2," No. Y4.L11/2:P49/2/976/pt2, CIS#
S541-82, page 168.
Buzzard, James A., 1976b. Letter from James A. Buzzard of
G.D. Searle to Dr. Alexander M. Schmidt, Commissioner,
U.S. Food and Drug Administration, January 7, 1976, "Good
Laboratory Practices" proposal enclosure, Reprinted in
U.S. Senate Joint Hearings before the Subcommittee on
Health of the Committee on Labor and Public Welfare and
the Subcommittee on Administrative Practice and Procedure
of the Committee on the Judiciary, "Preclinical and
Clinical Testing by the Pharmaceutical Industry, 1976,
Part 2," No. Y4.L11/2:P49/2/976/pt2, CIS# S541-82, page
185-213.
Cloninger, M.R., R.E. Balwin 1970. "Aspartylphenylalanine
methyl ester: a low calorie sweetener," Science, Volume
170, page 81.
Congressional Record 1982. "Orphan Drug Act," Congressional
Record, December 14, 1982, page 30445.
Congressional Record 1985a. "Saccharin Study and Labeling
Act Amendments of 1985," Congressional Record, Volume
131, No. 58, May 7, 1985, page S5489-S5519.
Congressional Record 1985b. "Aspartame Safety Act,"
Congressional Record, Volume 131, No. 106, August 1,
1985, page S10820-10847.
Farber, Steven A. 1989. "Aspartame and the Regulation of
Food Additives: A Study of FDA Decision-Making and a
Proposal for Change," Master of Science in Technology and
Public Policy Thesis at Massachusetts Institute of
Technology, Cambridge, MA 02139.
Federal Register 1973. Notice of Filing of Food Additive
Petition, G.D.Searle & Company. Federal Register, Volume
38, page 5,921.
Federal Register 1974. Volume 39, page 27137.
Federal Register 1975. Volume 40, page 56907, December 5,
1975.
Federal Register 1979. "Ruling on Objections and Notice of
Hearing Before a Public Board of Inquiry; Aspartame,"
Federal Register, Volume 44, page 31,717.
Federal Register 1981. "Aspartame: Commissioner's Final
Decision," Federal Register, Volume 46, page 38284-38308.
Federal Register 1983. "Food Additives Permitted for Direct
Addition to Food: Aspartame," 48(July 8): 31376-31382.
Federal Register 1984. "Food Additives Permitted for Direct
Addition to Food for Human Consumption; Aspartame,"
Volume 49, No. 36, February 22, 1984, page 6672-6682.
Food 1995. "Aspartame Adverse Reaction Reports Down in 1994
From 1985 Peak: FDA," Food Chemical News, June 12, 1995,
page 27.
Freeman, Martha, 1973. Memorandum from Martha A. Freeman,
Supervisory Medical Officer, FDA Division of Metabolic
and Endocrine Drug Products to Dr. C.J. Kokosi, FDA
Division of Toxicology, September 12, 1973, Reprinted in
US Senate 1987, page 326-336.
Furia, T.E. 1972. CRC Handbook of Food Additives. 2nd ed.,
Cleveland, Ohio: CRC Press, pp. 193.
GAO 1986. "Six Former HHS Employees' Involvement in
Aspartame's Approval," United States General Accounting
Office, GAO/HRD-86-109BR, July 1986.
GAO 1987. "Food Additive Approval Process Followed for
Aspartame," United States General Accounting Office,
GAO/HRD-87-46, June 1987.
Gordon, Gregory, 1987. "NutraSweet: Questions Swirl," UPI
Investigative Report, 10/12/87. Reprinted in US Senate
(1987, page 483-510).
Gordon, Gregory, 1996. "FDA resisted proposals to test aspartame,"
Minneapolis Star-Tribune, November 22, 1996.
Graves, Florence, 1984. "How Safe is Your Diet Soft Drink,"
Common Cause Magazine, July/August 1984. Reprinted in
Congressional Record (1985a, pages S5497-S5506)
Griffin, G. Edward, 1974. "World Without Cancer," America
Media, Westlake Village, California, ISBN 0-912986-09-3,
c1974, page 395. Quote from "Autopsy On The A.M.A.," San
Francisco Chronicle, January 2, 1970, page 42.
Gross, Adrian, 1975. Memorandum from Mr. Adrian Gross,
Scientific Investigations Staff to Mr. Carlton Sharp,
Chairman, Searle Investigation Task Force, September 29,
1975, Reprinted in U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1975, Part 1," No. Y4.L11/2:P49/2/975, CIS#
S541-16, page 440+.
Gross, Adrian, 1976b. Memorandum from Mr. Adrian Gross,
Scientific Investigations Staff to Mr. Carlton Sharp,
Chairman, Searle Investigation Task Force, March 15,
1976, Reprinted in U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 3," No. Y4.L11/2:P49/2/976/pt.3,
CIS# S541-12, page 310-376.
Gross, Adrian, 1985. Statement from Dr. Andrian Gross,
Former FDA Investigator and Scientist, "Aspartame Safety
Act," Congressional Record, Volume 131, No. 106, August
1, 1985, page S10835-S10840.
Gross, Adrian, 1987a. Letter from Dr. Andrian Gross, Former
FDA Investigator and Scientist to Senator Howard
Metzenbaum regarding pre-approval tests by G.D. Searle,
October 30, 1987, Reprinted in US Senate 1987, page 430-
439.
Gross, Adrian, 1987b. Letter from Dr. Andrian Gross, Former
FDA Investigator and Scientist to Senator Howard
Metzenbaum regarding pre-approval tests by G.D. Searle,
November 3, 1987, Reprinted in US Senate 1987, page 443-
453.
Helling, Herbert, 1970. Memorandum from Herbert Helling,
G.D. Searle Official to several G.D. Searle Officials,
regarding Food and Drug Sweetener Strategy, December 28,
1970, Reprinted in U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 2," No. Y4.L11/2:P49/2/976/pt2, CIS#
S541-82, page 16-19.
Kennedy, Edward M., 1976. Testimony of U.S. Senator Edward
M. Kennedy at the U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 3," No. Y4.L11/2:P49/2/976/pt.3,
CIS# S541-12.
Mazur, Robert, James Schlatter, Arthur Goldkemp 1969. "The
Structure-Taste Relationship of Some Dipeptides," Journal
of the Americna Chemical Society, Volume 91, No. 2, page
684.
Merrill, Richard, A., 1977. Memorandum from Richard A.
Merrill, Chief Counsel, Food and Drug Administration to
U.S. Attorney, Samuel K. Skinner, January 10, 1977,
Reprinted in Congressional Record 1985b, page S10827-
S10835.
Metzenbaum, Senator Howard, 1985. Testimony of U.S. Senator
Howard Metzenbaum of Ohio at "Aspartame Safety Act,"
Congressional Record, Volume 131, No. 106, August 1,
1985, page S10821.
Millman, Nancy, 1995. "King of the Tabletop," Chicago
Tribune, Sunday, September 17, 1995, page C1.
Monsanto 1990. "Monsanto Annual Report," 1990.
Monsanto 1991. "Monsanto Annual Report," 1991.
Monsanto 1992. "Monsanto Annual Report," 1992.
Monsanto 1993. "Monsanto Annual Report," 1993.
Monsanto 1994. "Monsanto Annual Report," 1994.
Mullarkey, Barbara, 1992. "Bittersweet Aspartame: A Diet
Delusion" by Barbara Alexander Mullarkey, NutriVoice,
P.O. Box 946, Oak Park, Illinois 60303, (708) 848-0116 begin_of_the_skype_highlighting ![]()
(708) 848-0116 FREE end_of_the_skype_highlighting.
Mullarkey, Barbara, 1994b. Account of John Cook as published
in Informed Consent Magazine. "How Safe Is Your
Artificial Sweetner" by Barbara Mullarkey,
September/October 1994. Available from Informed Consent
Magazine, P.O. Box 935, Williston, ND 58802-0935, 701/859-
3002. Available from NutriVoice, P.O. Box 946, Oak Park,
Illinois 60303, (708) 848-0116 begin_of_the_skype_highlighting ![]()
(708) 848-0116 FREE end_of_the_skype_highlighting.
Mullarkey, Barbara, 1995. Conversations between Mark D. Gold
and Barbara Mullarkey in 1995.
NutraSweet 1996. NutraSweet Internet Web Page:
http://www.nutrasweet.com/.
Olney, John W., et al., 1970. "Brain damage in infant mice
following oral intake of glutamate, aspartate or
cysteine," Nature, Volume 227, page 609-610.
Olney, John W. 1987. Letter from Dr. John W. Olney,
Neuropathologis, Washington University School of
Medicine, to Senator Howard M. Metzenbaum, December 8,
1987, Presented in the record before the U.S. Senate
Committee on Labor and Human Resources, November 3, 1987
regarding "NutraSweet Health and Safety Concerns."
Document # Y 4.L 11/4:S.HR6.100, page 468-476.
Olney, John W., Nuri Farber, Edward Spitznagel, Lee Robins,
1996. "Increasing Brain Tumor Rates: Is There a Link to
Aspartame?" Journal of Neuropathology and Experimental
Neurology, Volume 55, No. 11, Page 1115-1123.
Reynolds, W. Ann, N. Lemkey-Johnston, L.J. Filer, Jr., R.M.
Pitkin, 1971. "Monosodium Glutamate: Absence of
Hypothalamic Lesions After Ingestion by Newborn
Primates," Science, Volume 172, page 1342-1344.
Schmidt, Alexander M., 1976b. Statement by Alexander M.
Schmidt, Commissioner, U.S. Food and Drug Administration
before the U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 2," No. Y4.L11/2:P49/2/976/pt2, CIS#
S541-82, page 50-110.
Schmidt, Alexander M., 1976c. Statement by Alexander M.
Schmidt, Commissioner, U.S. Food and Drug Administration
before the U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 3," No. Y4.L11/2:P49/2/976/pt.3,
CIS# S541-12, page 3-56.
Searle 1975. "G.D. Searle Annual Report," 1975.
Searle, Daniel C. 1976a. Statement of Daniel C. Searle,
Chief Executive Officer, G.D. Searle & Co. before the
U.S. Senate Joint Hearings before the Subcommittee on
Health of the Committee on Labor and Public Welfare and
the Subcommittee on Administrative Practice and Procedure
of the Committee on the Judiciary, "Preclinical and
Clinical Testing by the Pharmaceutical Industry, 1976,
Part 2," No. Y4.L11/2:P49/2/976/pt2, CIS# S541-82, page
173-184.
Searle, Daniel C. 1976b. Letter from Daniel C. Searle, Chief
Executive Officer, G.D. Searle & Co., to U.S. Senator
Edward M. Kennedy, February 13, 1976, Reprinted in U.S.
Senate Joint Hearings before the Subcommittee on Health
of the Committee on Labor and Public Welfare and the
Subcommittee on Administrative Practice and Procedure of
the Committee on the Judiciary, "Preclinical and Clinical
Testing by the Pharmaceutical Industry, 1976, Part 2,"
No. Y4.L11/2:P49/2/976/pt2, CIS# S541-82, page 279-311.
Sharp, Carlton, 1975. Memorandum from Carlton Sharp and
Searle Investigation Task Force to the Searle
Investigation Steering Committee, December 8, 1975,
Reprinted in U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 2," No. Y4.L11/2:P49/2/976/pt2, CIS#
S541-82, page 24-28.
Stegink, Lewis D., Filer L., 1984a. "Aspartame: Physiology
and Biochemistry," Marcel Dekker, Inc., N.Y.
Stoddard, Mary Nash, 1995a. "The Deadly Deception" Compiled
by the Aspartame Consumer Safety Network for volumes of
available published information, ACSN, P.O. Box 780634,
Dallas, Texas 75378, (800) 969-6050 begin_of_the_skype_highlighting ![]()
(800) 969-6050 FREE end_of_the_skype_highlighting.
US Senate 1975. U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1975, Part 1," No. Y4.L11/2:P49/2/975, CIS#
S541-16.
US Senate 1976a. U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 2," No. Y4.L11/2:P49/2/976/pt2, CIS#
S541-82.
US Senate 1976b. U.S. Senate Joint Hearings before the
Subcommittee on Health of the Committee on Labor and
Public Welfare and the Subcommittee on Administrative
Practice and Procedure of the Committee on the Judiciary,
"Preclinical and Clinical Testing by the Pharmaceutical
Industry, 1976, Part 3," No. Y4.L11/2:P49/2/976/pt.3,
CIS# S541-12.
US Senate 1987. U.S. Senate Committee on Labor and Human
Resources, November 3, 1987 regarding "NutraSweet Health
and Safety Concerns." Document # Y 4.L 11/4:S.HR6.100.
USDA 1988. "1988 United States Department of Agriculture
Situation and Outlook Report; Sugar and Sweeteners."
Washington, DC: U.S. Government Printing Office, pp. 51.
Verrett, Jacqueline, 1987. Statement of Dr. Jacqueline
Verrett, Former Toxicologist, U.S. Food and Drug
Administration before U.S. Senate Committee on Labor and
Human Resources, November 3, 1987 regarding "NutraSweet
Health and Safety Concerns." Document # Y 4.L
11/4:S.HR6.100, page 383-390.
Wilson, Steve, 1985. "Sweet Suspicions," Television
broadcast and interviews regarding aspartame. Transcript
in Congressional Record (1985b, page S10826-S10827)
the news network 