Aspartame History: a short, 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… Preliminary 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 grand 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.
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.”
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 inadequacy 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 quantities 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 admitted 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 technicians,
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)
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 manufactured 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 that 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.”
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 submitted 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 laid 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.
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 mix-ups.
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
atand 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 undesirable 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, Burson 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
pre-approval 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.
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.
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.
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).
1996
On 27 June, 1996, Dr.
Kessler, without public notice, removed all restrictions on aspartame and
authorized its use in all products, including heated and baked goods. This was
done, knowing full well that aspartame breaks down into formaldehyde above 86
degrees F.
With this major
decision favorable to Monsanto, Searle, NutraSweet and all the rest who foist
this poison on the world population, Dr. Kessler departed the FDA making noises
about how victorous he was at slamming the tobacco industry. Subterfuge to the
very end!
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).
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.”]
______________________
*From DORWAY (http://dorway.com/history-of-aspartame)
______________________
*From DORWAY (http://dorway.com/history-of-aspartame)
The DORway to Discovery web site
was created in September of 1996 as a nonprofit site dedicated to informing the
public about the many unhealthy aspects of aspartame (a.k.a. Equal, Nutrasweet,
Spoonful, Equal Measure, Benevia, Joe Sweet, Nutrataste). It was created out of
frustration, stemming from the inability to motivate elected officials,
government officials and the media/medical system to inform the public and to
effect the removal of this substance from the human food chain.
DORway and thousands of other
anti-aspartame sites, are breaking down one of the greatest myths in America –
that aspartame is a safe sweetening agent and a useful weight-loss product.
This and similar sites are establishing a stance against aspartame, and the
tens of billions of dollars spent in propaganda activities promoting aspartame
as safe, desirable and useful activities.
This independently owned site (http://dorway.com/about-dorway/) seeks
only to inform. David Oliver Rietz is
founder of DORway.
References cited in this enclosure are available at www.holisticmed.com/aspartame
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