Bitter Truth, Part 4

5. History of Aspartame

Before we discuss the other hazardous aspects of aspartame, it can be
helpful to understand the sordid history behind the approval of
aspartame.

From the article:

“Numerous extensive, and very thorough, clinical
investigations have failed to reveal toxic side-
effects of aspartame. A review of over 100 animal
and human studies by the Council on Scientific
Affairs of the American Medical Association (AMA)
concluded that ‘Consumption of aspartame by normal
humans is safe and is not associated with serious
adverse health effects.’ (AMA 1985) Although the
AMA frequently errs in its conclusions about
nutrition, medicine, and health in general, I
believe they are accurate in the case of
aspartame.”

The article, which was printed in the Journal of the American Medical
Association (JAMA), was basically a summary of information provided by
the FDA. Considering the fact that the author published an article in a
book entitled “Stop the FDA” (Leibovitz 1992) and that the former Editor
of JAMA, Dr. Robert Moser is a long-time consultant for the NutraSweet
Company (Moser 1994, Roberts 1992), I find it difficult to understand
how the author could have taken the article seriously. After the
heading, “Council Report,” the article degenerates into little more than
a pro-aspartame fairy tale. Unfortunately, this fairy tale has turned
into a nightmare for countless individuals. What follows is a short, but
much more accurate history of aspartame.

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, 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
infromation 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 effect 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 test 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’tand didn’tcarry 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 therethe 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., University
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. Garden 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, the 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 99oF 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 S‹o 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).

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).

6. Aspartylphenylalanine Diketopiperazine (DKP)

The fact that Dr. Liebovitz did not even mention DKP, a chemical which
can sometimes be more prevalent than aspartame itself, is rather
distressing. At least one of the references he cites, AMA (1985)
discusses DKP at length, so he must be aware of this breakdown product.

Before aspartame was foisted upon the public, the amount of this
particular DKP in the diet was essentially zero (Federal Register 1983).
Therefore, no claim can automatically be made that DKP ingestion is
safe. Several quality studies would have to be performed in order to
conclude that DKP probably does not have a detrimental affect on humans.
No such quality studies have ever been done.

Most of the controversy surrounding DKP has involved the issue of brain
tumors and uterine polyps. While I will limit my discussion in this
section to cancer, there are two very important preliminary points that
need to be made:

a. Cancer is a very serious disease. However, there are
countless other serious diseases and therefore no reason
to limit the concern regarding DKP to cancer. The FDA
and EPA have approved numerous drugs and chemicals that
have unexpectedly caused or contributed to a wide range
of serious adverse reactions other than cancer. There is
no reason to believe that the possible detrimental
effects of DKP are limited to cancer. Dioxin is an
example of a chemical which was linked to cancer. Now it
turns out that the biggest issue is that dioxin has an
extremely deleterious effect on the immune system.

b. When looking at the aspartame and cancer issue, DKP
becomes a likely candidate for a possible cause.
However, it is only one of several possibilities.
Ingesting methanol or significant quantities of
racemized amino acids could be another cause or
contribuatory factor. Brain chemistry changes making one
slightly more susceptible to brain tumors caused by long-
term ingestion of aspartic acid and/or phenyalalnine
might be another possibility as to how aspartame could
contribute to brain cancer.

We will discuss the studies that show aspartame caused cancer in
laboratory animals later in this section. However, it should be
understood that the pre-approval studies were so poorly designed and
conducted that it would be impossible to conclude that aspartame is
safe. Some of the flaws which show that the FDA could not possibly have
concluded that aspartame does not cause cancer are as follows:

Lack of Statistical Power (simplified discussion of statistics) -
Aspartame is being regularly consumed by over 70 million people in the
U.S as discussed earlier. If aspartame was to cause cancerous tumors in
1% of the people who ingest it for several decades (as is what happens
with cigarettes), 700,000 people would develop such aspartame-caused
tumors in that time. A 5% tumor rate would lead to 3.5 million people
developing tumors. etc.

Let’s say, for arguments sake that aspartame causes cancerous tumors in
2% of the people in their lifetime. That’s 2% of 70 million people (in
the U.S.) or 1.4 million people. If I wanted to see if this was really
the case by testing aspartame in animals, I would feed aspartame to 70
million (test) animals. To another 70 million animals, I would give a
normal diet. If the aspartame-ingesting animals had 1.4 million
cancerous tumors more than the non-aspartame-ingesting (control)
animals, the cancer rate of aspartame would be 2%. Of course, it would
be impossible to conduct an experiment on this many animals.

So, instead of 70 million test animals and 70 million control animals, I
could use 1000 test animals and 1000 control animals. If the cancer rate
was 2%, there would be, in theory, 20 more cancerous tumors in the test
animals than in the control animals. If there was a 2% cancer rate for
aspartame, the reality is that each time I conducted the experiment, an
average of 20 more cancers in the test animals would appear than in the
control animals. If I ran the experiment ten times I may get something
like this:

Number of Excess Tumors in Test Animals
As Compared to Control Animals

Run #1 24
Run #2 14
Run #3 18
Run #4 22
Run #5 28
Run #6 19
Run #7 13
Run #8 20
Run #9 22
Run #10 20

As you can see, the numbers would vary, but the more times I conducted
the experiment, the closer the average of all of the runs would be to
20.

Instead of running the experiment on 1000 test animals and 1000 control
animals, a researcher may choose to use only 100 test animals and 100
control animals. If there was a 2% cancer rate for aspartame, there
would be an average of 2 more cancerous tumors for the test group as
opposed to the control group. However, since there are variations for
each experimental run, the results might look something like this for 10
runs (on 100 test animals and 100 control animals):

Test Group Control Group

Run #1 2 0
Run #2 4 1
Run #3 0 0
Run #4 3 0
Run #5 4 1
Run #6 0 2
Run #7 5 1
Run #8 3 1
Run #9 5 0
Run #10 0 0

The average over 10 runs is a 2% more cancer rate in the test group, but
there is a wide variations for each individual run.

As you can see, the smaller the group of animals used, the wider the
percentage variation for each run. Instead of 10 runs on 100 test
animals and 100 control animals, had I simply done a single run, the
results would likely be meaningless because there is such a wide
variation for a particular run with this few amount of animals. For
example, Run #9 shows 5 cancerous tumors in test animals and 0 in
control animals. Whereas Run #6 shows 0 cancerous tumors in test animals
and 2 cancerous tumors in control animals. Therefore, in order to more
accurately investigate whether aspartame causes a 2% cancer rate (1.4
million in 70 million users), I would have to use many times more than
100 animals or make numerous test runs with 100 animals each.

As you can see, if I was to use a small amount of animals, I could not
accurately determine whether there was a 2% cancer rate of aspartame. I
may be able to conclude that there is not a 20% cancer rate for
aspartame use (or 14 million cancers). If I can say that aspartame does
not cause 14 million cancers, that does not help me very much. It begs
the question as to whether it causes a 5% cancer rate, a 2% cancer rate
(1.4 million people) or a 0.2% cancer rate (140,000 people).

G.D. Searle used such a small number of animals in their experiments
relating to cancer that it would have been impossible to conclude that
aspartame was safe even had the experiments been conducted properly and
had there been no significant number of tumors found. FDA Chief of
Statistical Evaluations Branch, Satya D. Dubey stated the following in a
memo to the FDA Commissioner’s office (Farber 1989, page 101):

“From the design viewpoint, the probability of
observing a statistically significant result at 5%
significance level with 60 animals in the control
group and 40 animals in the treatment group when
the true difference in incidence rates of brain
tumors is not more than 5% would be less than
27.9% . . . Even 27.9% of statistical power will
generally be considered to be very low power. The
studies, E33/34 and E70, which I have
statistically reviewed, thus possess very low
power to detect true significant effect of the
kind stated above. . . . Therefore, their results
should not be considered confirmatory for decision
purposes.”

What Dr. Dubey is saying is that there is only a 27.9% liklihood that a
cancer rate of less than 5% would be found for the experiments discussed
above. A 4.9% cancer rate still amounts to 3,430,000 cancers in 70
million aspartame users! E33/34 and E70 are two studies which showed
that aspartame caused cancer in laboratory animals and will be discussed
later.

This is one of the tricks that is sometimes used in animals experiments.
If the researcher uses a small amount of animals, the study may not find
an increase in cancer rates for the test animal as opposed to the
control animal, but the lack of statistical power caused by the use of a
small number of animals made such a finding very unlikely.

When a researcher does use a small number of animals, the condition of
every single animal is very important. If even one animal’s cancer is
missed, the results of the experiment can be changed dramatically. Had
the studies E33/34 and E70 been run perfectly, there would have been a
27.9% chance that the researchers would have found a 5% or more tumor
rate. Since the experiments were so incredibly sloppy and the condition
of the animals was really a guess, it is likely that a 10% cancer rate
would have been missed.

G.D. Searle employees attempted to increase the statistical power of the
cancer studies by combining the results from different studies such as
E33/34 and E70 (Cornell 1984). E70 studies the effects of aspartame on
Charles River albino rat offspring by giving adding it to the mother’s
feed through the period of lactation and then the offspring’s feed until
death. The offspring were supposed to be examined at 104 weeks (or at
death). E33/34 was a chronic dosing study of aspartame given in four
different doses to rats for 104 weeks.

However, FDA Senior Statistician, Dr. Satya Dubey stated in1981 in a
memo to the FDA Commissioner’s science advisory team on aspartame
(Farber 1989, page 102):

“Since the protocol of E70 study is different, its
design is deficient, its data exhibit certain
peculiar patterns, and the statistical conclusions
derived from such data are much different from
that of the E33/34 study (compare the statistical
results of E33/34 and E70 studies), it does not
appear proper to me to combine the results of
these two studies.”

In his treatise on aspartame, Farber (1989, page 102) states in regards
to combining E33/34 and E70:

“I asked Myrto Lefkopoulou of the Harvard School
of Public Health, Biostatistics Department for her
comments on the statistical aggregation of E70 and
E33/34. She considered the aggregation of these
studies inappropriate because the effect of an in
utero study [E70] is different than a chronic
feeding study [E33/34]. …she stated that the in
utero study is looking for a teratogenic effect,
whereas the chronic feeding study was concerned
with carcinogenicity did aspartame promote
brain tumors?”

Farber points out that even if the results of these studies are
(improperly) combined, there is only a 67% chance that a 5% tumor rate
could be discovered (Farber 1989, page 103).

Continue to Part 5