- 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 neuroscienttists 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
preclinical 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 neoplasms
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 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 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:
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