- 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).
-
- 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."
-
- Today, hundreds of millions of Americans, and
millions more world-wide, consume foods and soft drinks stamped with
the NutraSweet "swirl", dump packets of Equal in their
coffee, and consume NutraSweet-flavored cereal, puddings, gelatins,
cheesecake, chewing gum, diet soft drinks, children's vitamins,
chilled juices, and 9,000 other products.
-
- So, what is aspartame, a.k.a. NutraSweet,
Spoonful, Equal...etc.? aspartyl phenylalanine-methyl ester.
-
- Aspartame (C14H18N2O5 ) is a compound of three
components. These components are methanol, aspartic acid and
phenylalanine (the latter being free form amino acids).
-
- Methanol (methyl alcohol or wood alcohol) is a
colorless, poisonous, and flammable liquid. It is used for making
formaldehyde, acetic acid, methyl t-butyl ether (a gasoline
additive), paint strippers, carburetor cleaners for your car's
engine, and chloromethanes, et al. This poison can be inhaled from
vapors, absorbed through the skin, and ingested.
-
- Methanol is the type of alcohol you read about
when people become blind from drinking it. In aspartame, methanol
poisoning and poisoning from methanol's breakdown components
(formaldehyde and formic acid) can have widespread and devastating
effects. This occurs in even small amounts, and is especially
damaging when introduced with toxic, free-form amino acids, called
excitotoxins.
-
- Methanol is quickly absorbed through the
stomach and small intestine mucosa. The methanol is converted into
formaldehyde (a known carcinogen). Then, via aldehyde hydrogenase,
the formaldehyde is converted to formic acid. These two metabolites
of methanol are toxic and cumulative.
-
- Phenylalanine is an amino acid. Well, amino
acids are good for us, right? Don't they keep us healthy? The answer
is yes, amino acids are necessary for good health, EXCEPT when you
separate the individual amino acid from its protein chain, and use
it as an "isolate" or by itself.
-
- The Aspartic acid, in aspartame, is also an
excitotoxin. An excitotoxin, is a deleterious substance that excites
or over-stimulates nerve cells. This occurs in the brain, as well as
the peripheral nerves, because aspartic acid, in free form, is an
absorption accelerant & easily crosses the blood-brain barrier.
-
- This pathological excitation of nerve cells
creates a breakdown of nerve function, as we will see. Basically,
they are a group of compounds that can cause special neurons within
the nervous system to become overexcited to the point that these
cells will die.
-
- That's right, they are excited to death.
Excitotoxins include such things as monosodium glutamate (MSG),
aspartate, (a main ingredient in NutraSweet), L-cysteine (found in
hydrolyzed vegetable protein) and related compounds.
-
- What makes this all the more intriguing is that
"excitotoxins" appear to play a key role in degenerative
nervous system diseases such as Parkinson's disease, Alzheimer's
disease, Huntington's, ALS (Lou Gehrig's disease) and many others.
-
- But the story doesn't stop there. It appears
that an imbalance of these excitotoxins during critical periods of
brain development can result in an abnormal formation of brain
pathways; that is, a "miswiring of the brain." This may
lead to serious disorders such as behavioral problems
(hyperactivity, aggression, attention deficit disorders, learning
disorders, poor learning ability, and ADD)-and a lifetime of
endocrine problems such as menstrual difficulties, infertility, and
premature puberty.
-
- One of the earliest observations seen in
animals exposed to large doses was gross obesity. Some neuroscientists
have voiced concern that America's explosion of childhood obesity
may be related to excitotoxins in food.
-
- Aspartame creates altered brain function, nerve
damage, and systemic organ complications. Information collected
reveals that aspartame clinically exacerbates any borderline (even
yet undetected) predisposing illness, and absolutely complicates
certain known medical illnesses like Lupus, Multiple Sclerosis,
Parkinson's, diabetes, retinopathies, allergies, mentation
disorders, etc. (See list of symptoms 1)
-
- Aspartame is a toxin, and is unique in this
hazardous respect. This in NOT an allergic reaction, but rather a
true toxin. No other food can be provided as a comparison to the
toxic nature of NutraSweet. Upon closer examination, the available
research revealed that the manufacturer (Monsanto) and the FDA are
manipulating the public (via the media) into thinking that aspartame
is safe. It is not. As an American who trusted the system we all
created, as an American who worked for the system, it made me angry
that public health has taken a backseat to greed. This is the
"engine" that perpetuated this epidemic: the collusion of
our government with multi-national conglomerate influence.
-
- G.D. Searle approached Dr. Harry Waisman,
Biochemist, Professor of Pediatrics, Director of the University of
Wisconsin's Joseph P. Kennedy Jr. Memorial Laboratory 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.
-
- G.D. Searle denied knowledge of or involvement
with the initiation, design or performance of the study. Yet, 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.
-
- The FDA banned the sweetener cyclamate, 1969.
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."
-
- 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).
Dr. John W. Olney informed G.D. Searle that aspartic acid caused
holes in the brains of mice.
-
- Ann Reynolds, a researcher who was hired by
G.D. Searle and who has done research for the Glutamate (MSG)
Association, and was asked to confirm Dr. Olney's tests. Dr.
Reynolds confirmed aspartame's neurotoxicity in infant mice.
-
- Excitotoxic compounds like MSG, aspartate,
cysteine seem to create hypothalamic lesions, particularly in young
animals. The reason for the latter is likely the fact that the blood
brain barrier closes most slowly (if ever completely) around
structures like hypothalamus. The outcome for such animals (rats)
was obesity, severe behavioral changes, etc.
-
- 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).
-
- An internal G.D. Searle memo laid out the
strategy for getting aspartame approved (Helling 1970):
- At this meeting [with FDA officials], the basic
philosophy 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.
- (Refer to Actual Letter...2)
-
- 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)
-
- 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 Department.
-
- 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.
-
- 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...."
-
- 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 adequacy of the information
submitted 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.
-
- Matalon said, "Let us say cigarettes were
invented today, and you give 20 people two packs a day and after six
weeks, no one has cancer, would you safe that it was safe? That's
what they did with NutraSweet."
-
- 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 or 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 bioavailability 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.
- (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 information or pre-clinical data were
provided.
-
- Such deficiencies in each area of required
information precluded a scientific evaluation of the clinical safety
of this product...."
-
- 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 representative's claim that Olney's
data raises no health concerns.
-
- On July 26, 1974, just 15 months after Searle
petitioned for approval, FDA commissioner Alexander Schmidt approved
aspartame use in dry foods, allowing a 30-day period for public
hearings and comment. He acted on a strong endorsement from the
Bureau of Foods, now called the Center for Food Safety and Applied
Nutrition (CFSAN).
-
- 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.
-
- At that point, consumer attorney Turner, author
of a 1970 book about food additives, objected to the short comment
period.
-
- Turner was joined in his protest by a
now-defunct public interest group and by Dr. John Olney, a
Washington University neuropathologist who had linked aspartame to
brain lesions in mice.
-
- Schmidt promptly froze the approval. In an
action that was the first of its kind, he ordered that a Public
Board of Inquiry be named to look into aspartame. Schmidt also had
been alerted to conflicts between Searle research reports and
conclusions from independent animal studies that the firm's
anti-infective drug, Flagyl and its cardiovascular drug Aldactone
may cause cancer. He named a Bureau of Drugs task force to
investigate.
-
- Philip Brodsky, the unit's since-retired lead
investigator, said aspartame was included in a broad inquiry into
Searle animal studies on five drugs and the Copper-7 intrauterine
device to surprise the company. "We didn't think they'd expect
us to cover it."
-
- The task force assailed Searle's conduct of
research on most of the products, including aspartame, in a searing,
84-page report.
-
- "At the heart of the FDA's regulatory
process," the report said, "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 G.D. Searle Co., we have no basis for such reliance now."
-
- The task force charged, for example, that the
company removed tumors from live animals and stored animal tissues
in formaldehyde for so long that they deteriorated. Instead of
performing autopsies on rhesus monkeys that suffered seizures after
being fed aspartame, the company had financed a new monkey study
with a different methodology that showed no problems.
-
- For the next seven years, Searle's petition was
tied up in reviews by the task force and other sharply critical FDA
panels.
-
- At the task force's request, Richard Merrill,
the FDA's general counsel, demanded in a letter that Samuel Skinner,
the U.S. attorney in Chicago, open a grand jury investigation of
Searle and three of its employees.
-
- One Searle official named by Merrill was Robert
McConnell, who had been director of Searle's Department of Pathology
and Toxicology and oversaw most of the company's aspartame research.
-
- McConnell's Detroit lawyer, Gerald Wahl, said
that as the inquiries heated up, his client was suddenly awarded a
$15,000 bonus and asked to take a three-year sabbatical by director
Wesley Dixon. Wahl said Dixon told McConnell he had become a
"political liability," a remark Dixon later denied making.
-
- McConnell received his annual salary of more
than $60,000 during the sabbatical at the Massachusetts Institute of
Technology, but he never got his job back, and ended up suing the
company, Wahl said.
-
- "I've represented hundreds of executives,
but I've never seen anybody get the deal that McConnell got,"
he said. "When you boil it all down, they were looking for
continued support from McConnell during the inquiries."
-
- 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 (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)
-
- Consumer lawyer Turner said, "The notion
that an industrial company would take large sums of money and parcel
it out to scientific consulting firms and university departments,
who they consider to be personal and commercial allies is an
unconscionable way to ensure the safety of the American food
supply."
-
- He said the NutraSweet experience shows that
"the entire system of the way scientific research is done needs
to be carefully investigated, evaluated, and revamped."
-
- Food industry officials also said most studies
financed by Searle or the NutraSweet Co. have been arranged as
contracts, rather than grants. Smith said the company often uses
contracts "to accomplish a specific research task."
-
- James Scala, former director of health sciences
for the General Foods Corp., a major NutraSweet user, said that a
scientist working under contract became "more of an arm of the
Searle research group than a grantee."
-
- 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).
-
- Chief investigator Brodsky said that
"politicized" handling of the task force disclosures, at
hearings chaired by Sen. Edward Kennedy D-Mass., was one reason he
retired in 1977. 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.
-
- 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).
-
- 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.
-
- 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 alleging 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 submitted 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:
- * "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 neoplasm's as well as other lesions." (Gross 1987a, page
8).
- * 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)
- * "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)
- * "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)
- * Animals which had died were sometimes
recorded as being alive and vice 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)
- * "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.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)
- * "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)
- * "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."
- * "In each study investigated, poor
practices, inaccuracies, and discrepancies were noted in the
antemortem phases which could compromise the study."
- * "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)
- * Animals were not removed from the room during
the twice per month exterminator sprayings. (Gross 1985, page S10836
of Congressional Record 1985b)
- * 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."
- * 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.
- * "Contrary to protocol, slides were not
prepared of this [unusual lesions from the Aspartame (DKP) study)
tissue for microscopic examinations . . . .."
- * "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)
-
- "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)
- * "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."
- * [There were] "clerical or arithmetic
errors which resulted in reports of fewer tumors."
- * [G.D. Searle] "delayed the reporting of
alarming findings." FDA Toxicologist and Task Force member, Dr.
Andrian Gross stated:
-
- "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.
-
- 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 reproductive studies submitted to the FDA; (as noted
in the Congressional record)
- "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 re-summarization 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 abysmal.
-
- 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 page (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 (Se. Ted 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 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:
- * 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.
- * 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.
- * 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.
- * 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.
-
- 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.
-
|