5. History of Aspartame Before we discuss the other hazardous aspects of aspartame, it can be helpful to understand the sordid history behind the approval of aspartame. From the article: "Numerous extensive, and very thorough, clinical investigations have failed to reveal toxic side- effects of aspartame. A review of over 100 animal and human studies by the Council on Scientific Affairs of the American Medical Association (AMA) concluded that 'Consumption of aspartame by normal humans is safe and is not associated with serious adverse health effects.' (AMA 1985) Although the AMA frequently errs in its conclusions about nutrition, medicine, and health in general, I believe they are accurate in the case of aspartame." The article, which was printed in the Journal of the American Medical Association (JAMA), was basically a summary of information provided by the FDA. Considering the fact that the author published an article in a book entitled "Stop the FDA" (Leibovitz 1992) and that the former Editor of JAMA, Dr. Robert Moser is a long-time consultant for the NutraSweet Company (Moser 1994, Roberts 1992), I find it difficult to understand how the author could have taken the article seriously. After the heading, "Council Report," the article degenerates into little more than a pro-aspartame fairy tale. Unfortunately, this fairy tale has turned into a nightmare for countless individuals. What follows is a short, but much more accurate history of aspartame. 1964 ---- The development of new pharmaceuticals was the focus of research at the international pharmaceutical company, G.D. Searle and Company (Farber 1989, page 29). A group working on an ulcer drug was formed including Dr. Robert Mazer, James Schlatter, Arthur Goldkemp and Imperial Chemical. In particular, they were looking for an inhibitor of the gastrointestinal secretory hormone gastrin (Stegink 1984a, page 3). 1965 ---- In 1965, while creating a bioassay, an intermediate chemical was synthesized -- aspartylphenylalanine-methyl-ester (aspartame). In December of 1965, while James Schlatter was recrystalling aspartame from ethanol, the mixture spilled onto the outside of the flask. Some of the powder got onto his fingers. Later, when he licked his fingers to pick up a piece of paper, he noticed a very strong sweet taste. He realized that the sweet taste might have been the aspartame. So, believing that the dipeptide aspartame was not likely to be toxic, he tasted a little bit and discovered its sweet taste (Stegink 1984a, page 4). The discovery was reported in 1966, but there was no mention of the sweetness (Furia 1972). 1969 ---- The investigators first reported the discovery of the artificial sweetener in the Journal of the American Chemical Society stating (Mazur 1969): "We wish to report another accidental discovery of an organic compound with a profound sucrose (table sugar) like taste . . . Prelminary tasting showed this compound to have a potency of 100-200 times sucrose depending on concentration and on what other flavors are present and to be devoid of unpleasant aftertaste." -------------- In 1969, former Commissioner of the FDA, Dr. Herbert L. Ley was quoted as follows (Griffin 1974): "The thing that bugs me is that people think the Food and Drug Administration (FDA) is protecting them -- it isn't. What the FDA is doing and what the public thinks it's doing are as different as night and day." 1970 ---- The discovery of aspartame is reported in the well-known publication, Science (Cloninger 1970). -------------- G.D. Searle approached Dr. Harry Waisman, Biochemist, Professor of Pediatrics, Director of the University of Wisconsin's Joseph P. Kennedy Jr. Memorial Laboroatory of Mental Retardation Research and a respected expert in phenylalanine toxicity, to conduct a study of the effects of aspartame on primates. The study was initiated on January 15, 1970 and was terminated on or about April 25, 1971. Dr. Waisman died unexpectedly in March, 1971. Seven infant monkeys were given aspartame with milk. One died after 300 days. Five others (out of seven total) had grad mal seizures. The actual results were hidden from the FDA when G.D. Searle submitted its initial applications (Stoddard 1995a, page 6; Merrill 1977; Graves 1984, page S5506 of Congressional Record 1985a; Gross 1976b, page 333 of US Senate 1976b). G.D. Searle denied knowledge of or involvement with the initiation, design or performance of the study. Yet, the false results were submitted to the FDA like the rest of the 150 G.D. Searle studies (on aspartame and other products), bearing a Searle Pathology-Toxicology project number. Both Dr. Waisman and G.D. Searle were responsible for the study design. A number of false statements were made by G.D. Searle including that the animals were unavailable for purchase for autopsy after the termination of the study. -------------- Neuroscientist and researcher John W. Olney found that oral intake of glutamate, aspartate and cysteine, all excitotoxic amino acids, cause brain damage in mice (Olney 1970). -------------- An internal G.D. Searle memo layed out the strategy for getting aspartame approved (Helling 1970): At this meeting [with FDA officials], the basic philospohy of our approach to food and drugs should be to try to get them to say "Yes," to rank the things that we are going to ask for so we are putting first those questions we would like to get a "yes" to, even if we have to throw some in that have no significance to us, other than putting them in a yes saying habit. We must create affirmative atmosphere in our dealing with them. It would help if we can get them or get their people involved to do us any such favors. This would also help bring them into subconscious spirit of participation. -------------- The FDA banned the sweetener cyclamate. Robert Scheuplein, who was the acting Director of FDA's Toxicological Services Center for Food Safety and Applied Nutrition was quoted as saying "the decision was more a matter of politics than science." (Stoddard 1995a, page 7) 1971 ---- Ann Reynolds, a researcher who was hired by G.D. Searle and who has done research for the Glutamate (MSG) Association, confirmed aspartame's neurotoxicity in infant mice (Reynolds 1971). -------------- Dr. John W. Olney informed G.D. Searle that aspartic acid caused holes in the brains of mice. G.D. Searle did not inform the FDA of this study until after aspartame's approval. None of the tests submitted by G.D. Searle to the FDA contradicted these findings (Olney 1970, Gordon 1987, page 493 of US Senate 1987). 1972 ---- FDA Toxicologist Dr. Adrian Gross came upon some irregularities in the submitted tests of the G.D. Searle drug Flagyl. G.D. Searle did not respond for another two years. Their response raised serious questions about the validity of their tests (Gross 1975, page 35; Schmidt 1976b, page 6). 1973 ---- On March 5, 1973, G.D. Searle's petition to the FDA for approval to market aspartame as a sweetening agent was published in the Federal Register (1973). -------------- On March 21, 1973 the MBR report was submitted to G.D. Searle. Background In August of 1970, G.D. Searle conducted two 78- week toxicity studies on rats for what was to become a best-selling heart medication, Aldactone. One study was conducted at G.D. Searle and one at Hazelton Laboratories. In March 1972, the rats for autopsied and the pathology slides were analyzed. For confirmation of the results, G.D. Searle sent the slides to Biological Research, Ltd. where board certified pathologist, Dr. Jacqueline Mauro examined the data. She discovered that the drug appeared to induce tumors in the liver, testes, and thyroid of the rats. The report submitted to G.D. Searle by Dr. Mauro was known as the MBR Report. These statistically significant findings were confirmed by G.D. Searle's Mathematics-Statistics Departement. Instead of submitting these alarming findings to the FDA, G.D. Searle contracted with another pathologist, Dr. Donald A. Willigan. He was given 1,000 slides to examine. The Willigan Report was more to G.D. Searle's liking because it revealed a statistically significant increase in thyroid and testes tumors, but not in liver tumors. Liver tumors are of much more concern to the FDA. The Willigan Report was immediately submitted to the FDA. G.D. Searle did not disclose the MBR Report to the FDA until August 18, 1975, 27 months after it had been given to G.D. Searle (Schmidt 1976b, page 14, Merrill 1977, page S10828-S10831). At first, G.D. Searle claimed that they did not submit the MBR Report to the FDA because of an "oversight." Later, they claimed that Dr. Mauro's MBR report was not submitted because they did not like the terminology Dr. Mauro used in evaluating the thyroid slides. They claimed that her inaccurate terminology in this case showed that Dr. Mauro was unreliable as a pathologist. Yet, G.D. Searle never notified Dr. Mauro of any questions and on June 1, 1973, they wrote to MBR and stated that the report "looks just fine" (Merrill 1977). -------------- The FDA Commissioner from 1972 to 1976, Alexander Schmidt, M.D. felt that "Superficially, it seemed like, if there would ever be a safe kind of product, that would be it. The idea that two naturally-occurring amino acids could harm someone in relatively small amounts...." (Mullarkey 1992, page 15) -------------- In an FDA memorandum dated September 12, 1973, Martha M. Freeman, M.D. of the FDA Division of Metabolic and Endocrine Drug Products addressed the adequecy of the information submited by G.D. Searle in their petition to approve aspartame (Freeman 1973): "Although it was stated that studies were also performed with diketopiperazine [DKP] an impurity which results from acid hydrolysis of Aspartame, no data are provided on this product." Commenting on one particular single dose study: "It is not feasible to extrapolate results of such single dose testing to the likely condition of use of Aspartame as an artificial sweetener." It is important to note that Dr. Freeman pointed out the inadequency of single-dose tests of aspartame as early as 1973. Since then, the NutraSweet Company has flooded the scientific community with single-dose studies. "Chemistry - No information is provided other than formulae for Aspartame and its diketo-piperazine." "Pharmacology - Reference is made to 2 year rat studies, but no data are provided on acute or chronic toxicity." "Clinical - No protocols nor curriculum vitae information are provided for the 10 completed clinical studies. Results are reported in narrative summary form, and tabulations of mean average values only. No information is given as to the identity of the reporting labs, methodology (except rarely), or normal values. (Reported units for several parameters cannot be verified at this time.) "No pharmacokinetic data are provided on absorption, excretion, metabolism, half-life; nor bioaviliability of capsule vs. food-additive administration." Dr. Freeman concludes: "1. The administration of Aspartame, as reported in these studies at high dosage levels for prolonged periods, constitutes clinical investigational use of a new drug substance." "2. The information submitted for our review is inadequate to permit a scientific evaluation of clinical safety." She went on to recommend that marketing of aspartame be contingent upon proven clinical safety of aspartame. The FDA Bureau of Foods rejected Dr. Freeman's recommendation (Graves 1984, page S5498 of Congressional Record 1985a). -------------- Construction of a large aspartame manufacturing plant in Augusta, Georgia was halted. It was thought that aspartame's uncertain regulatory future was the main reason for the stopping of construction (Farber 1989, page 47). In the 1973 G.D. Searle Annual Report, an executive stated that "commercial quanities of the sweetener will be supplied from the enlarged facility of Ajinomoto." Ajinomoto is the inventor and main producer of the food additive MSG. 1974 ---- Ninety of the 113 aspartame studies which were submitted by G.D. Searle to the FDA were conducted in the early to mid- 1970's. All of the tests that were described by the FDA as "pivotal" were conducted during this time. Eighty percent of these tests were conducted by G.D. Searle or by their major contractor, Hazleton Laboratories, Inc. (Graves 1984, page S5497 of Congressional Record 1985a). -------------- Dr. J. Richard Crout, the acting director of the FDA Bureau of Drugs stated that "The information submitted for our review was limited to narrative clinical summaries and tabulated mean values of laboratory studies. No protocols, manufacturing controls infromation or preclinical data were provided. Such deficiencies in each area of required infromation precluded a scientific evaluation of the clinical safety of this product...." (Mullarkey 1992, page 23) -------------- Dr. John Olney and Consumer Interest attorney, James Turner, Esq. met with G.D. Searle to discuss the results of Olney's experiments. G.D. Searle representatives claim that Olney's data raises no health concerns (Stoddard 1995a, page 7). -------------- The FDA approved aspartame for limited use on July 26, 1974. The allowable uses included free-flowing sugar substitute, tablets for sweetening hot beverages, cereals, gum, and dry bases (Farber 1989, Federal Register 1974). It was not approved for baking goods, cooking, or carbonated beverages. This approval came despite the fact that FDA scientists found serious deficiencies in all of the 13 tests related to genetic damage which were submitted by G.D. Searle. -------------- In August 1974, before aspartame could go on the market, Dr. John Olney, James Turner, and Label Inc. (Legal Action for Buyers' Education and Labeling) filed a formal objection stating that they believe aspartame could cause brain damage. They were particularly worried about aspartame's effects on children (Graves 1984, page S5498 of Congressional Record 1985a; Federal Register 1975, Olney 1987, page 3). -------------- G.D. Searle's responses to queries about the testing of their drug Flagyl, serious and unexpected side effect from other drugs they developed, and information from Dr. John Olney's studies started a controversy within the FDA as to the quality and validity of G.D. Searle's test of aspartame and pharmaceuticals (Graves 1984, page S5498 of Congressional Record 1985a). 1975 ---- In July 1975, the FDA Commissioner, Dr. Alexander Schmidt appointed a special Task Force to look at 25 key studies for the drugs Flagyl, Aldactone, Norpace, and the food additive aspartame. Eleven of the pivotal studies examined involved aspartame. All of the studies whether conducted at G.D. Searle or Hazleton Laboratories were the responsibility of the Pathology-Toxicology Department at G.D. Searle. (Gross 1987a, page 430 of US Senate 1987). The special Task Force was headed by Philip Brodsky, FDA's Lead Investigator and assisted by FDA Toxicologist, Dr. Adrian Gross. The Task Force was especially interested in "pivotal" tests as described in an article from Common Cause Magazine by Florence Graves (Graves 1984, page S5499 of Congressional Record 1985a): "Before the task force had completed its investigation in 1976, Searle had submitted the vast majority of the more than 100 tests it ultimately gave the FDA in an effort to get aspartame approved. These included all test ever described as 'pivotal' by the FDA. About half the pivotal tests were done at Searle; about one-third were done at Hazleton Laboratories. 'Pivotal' tests include long-term (two-year) tests such as those done to determine whether aspartame might cause cancer. Former FDA commissioner Alexander Schmidt said in a recent interview that if a pivotal test is found to be unreliable, it must be repeated 'Some studies are more important than others, and they have to be done impeccably,' Schmidt said." -------------- G.D. Searle executives admited to "payments to employees of certain foreign governments to obtain sales of their products." (Searle 1975) -------------- On July 10, 1975, Senator Edward Kennedy chaired a hearing on drug-related research before the Senate Subcommittee on Health of the Committee on Labor and Public Welfare (US Senate 1975). Preliminary reports of discrepancies discovered about G.D. Searle were discussed. The findings of the FDA Task Force were later presented at further hearings on January 20, 1976 (US Senate 1976a) and April 8, 1976 (US Senate 1976b). -------------- On December 5, 1975, Dr. John Olney and James Turner waived their right to a hearing at the suggestion of the FDA General Counsel after the FDA and G.D. Searle agreed to hold a Public Board Of Inquiry (PBOI) (Federal Register 1975, page 286, Mullarkey 1994b, page 5-6). -------------- On December 5, 1975, the FDA put a hold on the approval of aspartame due to the preliminary findings of the FDA Task Force. The Public Board of Inquiry is also put on hold (Mullarkey 1994b, page 5-6; Federal Register 1975). The evidence of the aspartame pivotal studies were protected under FDA seal on December 3, 1975 (Sharp 1975). -------------- G.D. Searle had invested 19.7 million dollars in an incomplete production facility and 9.2. million dollars in aspartame inventory. On December 8, 1975, stockholders filed a class action lawsuit alledging that G.D. Searle had concealed information from the public regarding the nature and quality of animal research at G.D. Searle in violation of the Securities and Exchange Act (Farber 1989, page 48). 1976 ---- On January 7, 1976, G.D. Searle submited to the FDA their proposal for the adoption of "Good Laboratory Practices" (Buzzard 1976b). G.D. Searle's input was used in FDA's adoption of Good Laboratory Practices. -------------- In March 1976, the FDA Task Force completed a 500-page report with 15,000 pages of exhibits (80-page summary) to the FDA after completing their investigation (Schmidt 1976c, page 4 of US Senate 1976b). -------------- A preliminary statement about the breadth of the investigation from FDA Toxicologist and Task Force team member, Dr. Andrian Gross before the US Senate (Gross 1987a, page 1-2): "Practices that were noted in connection with any given such study were quite likely to have been noted also for other studies that were audited, and this was a situation which was in no way unexpected: after all, the set of all such studies executed by that firm from about 1968 to the mid- 1970's were conducted in essentially the same facilities, by virtually the same tehnicians, professional workers and supervisors, and the nature of such studies does not differ much whether a food additive or a drug product is being tested for safety in laboratory animals. It is in this sense, therefore, that the overall conclusion summarized at the beginning of the Searle Task Force Report have relevance to all the studies audited in 1975 (whether they had references to aspartame or to any of the six drug products of Searle's) and, by extension, to the totality of experimental studies carried out by that firm around that time -- 1968 to 1975." A few of the conclusions of the FDA Task Force (Gross 1987a, page 2-3): "At the heart of FDA's regulatory process is its ability to rely upon the integrity of the basic safety data submitted by sponsors of regulated products. Our investigation clearly demonstrates that, in the (case of the) GD Searle Company, we have no basis for such reliance now." "We have noted that Searle has not submitted all the facts of experiments to FDA, retaining unto itself the unpermitted option of filtering, interpreting, and not submitting information which we would consider material to the safety evaluation of the product . . . Finally, we have found instances of irrelevant or unproductive animal research where experiments have been poorly conceived, carelessly executed, or inaccurately analyzed or reported." "Some of our findings suggest an attitude of disregard for FDA's mission of protection of the public health by selectively reporting the results of studies in a manner which allay the concerns of questions of an FDA reviewer." "Unreliability in Searle's animal research does not imply, however, that its animal studies have provided no useful information on the safety of its products. Poorly controlled experiments containing random errors blur the differences between treated and control animals and increase the difficulty of discriminating between the two populations to detect a product induced effect. A positive finding of toxicity in the test animals in a poorly controlled study provides a reasonable lower bound on the true toxicity of the substance. The agency must be free to conclude that the results from such a study, while admittedly imprecise as to incidence or severity of the untoward effect, cannot be overlooked in arriving at a decision concerning the toxic potential of the product." A few of the relevant findings summarized from various documents describing the FDA Task Force Report: a. "Excising masses (tumors) from live animals, in some cases without histologic examination of the masses, in others without reporting them to the FDA." (Schmidt 1976c, page 4 of US Senate 1976b) Searle's representatives, when caught and questioned about these actions, stated that "these masses were in the head and neck areas and prevented the animals from feeding." (Buzzard 1976a) "Failure to report to the FDA all internal tumors present in the experimental rats, e.g., polyps in the uterus, ovary neoplasms as well as other lesions." (Gross 1987a, page 8). b. G.D. Searle "stored animal tissues in formaldehyde for so long that they deteriorated." (Gordon 1987, page 496 of US Senate 1987; US Schmidt 1976c, page 25, 27 of US Senate 1976b) c. "Instead of performing autopsies on rhesus monkeys that suffered seizures after being fed aspartame, the company had financed a new monkey seizure study with a different methodology that showed no problems." (Gordon 1987, page 496 of US Senate 1987) d. "Reporting animals as unavailable for necropsy when, in fact, records indicate that the animals were available but Searle choose not to purchase them." (Schmidt 1976c, page 5 of US Senate 1976b) e. Animals which had died were sometimes recorded as being alive and vica versa. "These include approximately 20 instances of animals reported as dead and then reported as having vital signs normal again at subsequent observation periods." (Gross 1985, page S10835) f. "Selecting statistical procedures which used a total number of animals as the denominator when only a portion of the animals were examined, thus reducing the significance of adverse effects." (Schmidt 1976c, page 4 of US Senate 1976b) g. G.D. Searle told the FDA that 12 lots of DKP were manufacturered and tested in one study, yet only seven batches were actually made. (Gross 1985, page S10835) h. "Significant deviations from the protocols of several studies were noted which may have compromised the value of these studies . . . In at least one study, the Aspartame 52 weeks monkey study, the protocol was written after the study had been initiated." (Gross 1985, page S10835) i. "It is significant to note that the Searle employee responsible for reviewing most of the reproduction studies had only one year of prior experience, working on population dynamics of cotton tail rabbits while employed by Illinois Wildlife Service. In order to prepare him for this title of 'Senior Research Assistant in Teratology' (fetal damage) Searle bought him books to read on the subject and also sent him to a meeting of the Teratology Society. This qualified him to submit 18 of the initial tests to the FDA, in addition to training an assistant and 2 technicians. He certainly must have kept them busy because Searle claimed that 329 teratology examinations were conducted in just 2 days. He estimated that he himself examined about 30 fetuses a day, but officials for the Center for Food and Applied Nutrition could never determine how that was possible." (Stoddard 1995a, page 9; Graves 1984, page S5500 of Congressional Record 1985a) j. "In each study investigated, poor practices, inaccuracies, and discrepancies were noted in the antemortem phases which could compromise the study." (Gross 1985, page S10836 of Congressional Record 1985b) k. "Presenting information to FDA in a manner likely to obscure problems, such as editing the report of a consulting pathologist . . . Reporting one pathology report while failing to submit, or make reference to another usually more adverse pathology report on the same slide." (Schmidt 1976c, page 4-5 of US Senate 1976b) l. Animals were not removed from the room during the twice per month exterminator sprayings. (Gross 1985, page S10836 of Congressional Record 1985b) m. Often the substance being tested which was given to the animals was not analyzed or tested for homogeneity. "No records were found to indicate that any treatment mixtures used in the studies were ever tested or assayed for pesticide content . . . Running inventory records for either treatment mixtures or the test compounds used in treatment mixtures are not maintained." (Gross 1985, page S10836 of Congressional Record 1985b) n. In the Aspartame (DKP) 115 week rat study the written observations of the pathology report was changed by the supervising pathologist, Dr. Rudolph Stejskal even though he was not physically present during the autopsies and could not have verified the observations of the pathologist who did perform the autopsies. The pathologist who did perform some of the autopsies had no formal training for such procedures. (Gross 1985, page S10837 of Congressional Record 1985b) o. "Contrary to protocol, slides were not prepared of this [unusual lesions from the Aspartame (DKP) study) tissue for microscopic examinstions . . . ." (Gross 1985, page S10837 of Congressional Record 1985b) p. "In the Aspartame 46 weeks hamster study, blood samples reported in the submission to FDA as 26 week values (for certain specified animals) were found by our investigators as being, in fact, values for different animals which were bled at the 38th week. Many of the animals for which these values were reported (to the FDA) were dead at the 38th week." (Gross 1985, page S10838 of Congressional Record 1985b) "It is apparent from the report, that the Appendix portion contains all the individual (animal) values of clinical lab data available from the raw data file. A selected portion of these values appears to have been used in computing group means (which were reported to the FDA). It is not clear what criteria may have been used for selecting a portion of the data or for deleting the others in computing the means (reported to the FDA)." (Gross 1985, page S10838 of Congressional Record 1985b) q. "Searle technical personnel failed to adhere to protocols, make accurate observations, sign and date records, and accurately administer the product under test and proper lab procedures." (Farber 1989, page 109) r. [There were] "clerical or arithmetic errors which resulted in reports of fewer tumors." (Schmidt 1976c, page 27 of US Senate 1976b) s. [G.D. Searle] "delayed the reporting of alarming findings." (Schmidt 1976c, page 27 of US Senate 1976b) FDA Toxicologist and Task Force member, Dr. Andrian Gross stated (Wilson 1985): "They [G.D. Searle] lied and they didn't submit the real nature of their observations because had they done that it is more than likely that a great number of these studies would have been rejected simply for adequacy. What Searle did, they took great pains to camouflage these shortcomings of the study. As I say filter and just present to the FDA what they wished the FDA to know and they did other terrible things for instance animals would develop tumors while they were under study. Well they would remove these tumors from the animals." FDA Lead Investigator and Task Force Team Leader, Phillip Brodsky described the 1975 FDA Task Force members as some of the most experienced drug investigators. He went on to state that he had never seen anything as bad as G.D. Searle's studies (Graves 1984, page S5499 of Congressional Record 1985a). The report quoted a letter written to G.D. Searle on July 15, 1975 from its consultant in reproduction and teratology, Dr. Gregory Palmer, in regards to a review of some of G.D. Searle's repreductive studies submitted to the FDA (Gross 1985, page S10838 of Congressional Record 1985b): "Even following the track you did, it seems to me you have only confounded the issue by a series of studies most of which have severe design deficiencies or obvious lack of expertise in animal management. Because of these twin factors, all the careful and detailed examination of fetuses, all the writing, summarization and resummarization is of little avail because of the shaky foundation." G.D. Searle officials noted that Dr. Palmer did not look at all of the teratology studies (Searle 1976b, page 21). However, there is no credible evidence that would lead a reasonable person to believe that the studies which were not presented to Dr. Palmer were much better. In fact, the evidence shows that it is very likely that all of the studies were abyssmal. The FDA Commissioner at the time, Alexander Schmidt stated (Graves 1984, page S5497 of Congressional Record 1985a): "[Searle's studies were] incredibly sloppy science. What we discovered was reprehensible." Dr. Marvin Legator, professor and director of environmental toxicology at the University of Texas and the pioneer of mutagenicity testing at the FDA from 1962 to 1972 was asked by Common Cause Magazine to review the FDA investigation results of G.D. Searle's tests (Graves 1984, page S5498 of Congressional Record 1985a): "[All tests were] scientifically irresponsible [and] disgraceful. I'm just shocked that that kind of sloppy [work] would even be sent to FDA, and that the FDA administrators accepted it. There is no reason why these tests couldn't have been carried out correctly. It's not that we are talking about some great scientific breakthrough in methodology." Senator Edward Kennedy at the April 8, 1976 hearings before the Senate Subcommittee on Labor and Public Welfare stated (Kennedy 1976): "The extensive nature of the almost unbelievable range of abuses discovered by the FDA on several major Searle products is profoundly disturbing." -------------- In January, 1976, G.D. Searle defended their results by claiming (Searle 1976a, page 5-6): "In all of the studies at Searle which have been examined by the FDA in its investigation, the scope of the material being considered included seven years of observation, from 1968 to date, in 57 studies involving more than 5,700 animals with over 228 million observations and calculations." However, their deliberate misconduct and "lies" (as put by FDA Investigator, Dr. Adrian Gross) invalidated their experiments for the following reasons: 1. Many of the problems with the studies included horrendous experimental designs, questions regarding dosage given, loss of animal tissue and data, etc., etc., which invalidates entire experiments and causes what they claim to be 4 million observations and calculations per study (average) to become irrelevant. 2. Only the key aspartame studies were looked at. It is almost a certainty that the non-key aspartame studies were equally flawed. Therefore, this would invalidate the "hundreds of millions" of observations and calculations made during these studies. 3. The difference between a study showing no statistical difference and a significant statistical difference is often only a few observations or calculations. Therefore, had the myriad of other serious experimental errors not occurred (as detailed above), the observation and calculation mistakes in each experiment investigated would, by themselves, invalidate most of the key studies. 4. It is highly unlikely that the FDA Investigative teams found all of the problems with G.D. Searle's studies. G.D. Searle seemed so intent on covering up their misconduct, that it is quite likely that they were able to hide many of the problems from the FDA. -------------- A series of poorly conceived, flawed studies funded by G.D. Searle were published in Volume 2 (1976) of the Journal of Toxicology and Environmental Health. An Associate Editor of this scientific journal was Robert G. McConnell, the Director of G.D. Searle's Department of Pathology and Toxicology (the department responsible for monitoring the quality of G.D. Searle's pre-approval tests investigated by the 1975 FDA Task Force). Mr. McConnell's story continues later in 1977. Another G.D. Searle employee, Carl R. Mackerer was an editor of the journal. Another editor of the journal was Thomas R. Tephly, the person responsible for conducting a series of badly flawed blood methanol and formate measurements in NutraSweet-funded studies over the last 15 years. -------------- In July 1976, the FDA decided to investigate 15 key aspartame studies submited by G.D. Searle in which the 1975 FDA Task Force discovered problems. Three (3) of the studies were investigated at the FDA (E5, E77/78, E89) by a 5-member Task Force headed by FDA veteran Inspector, Jerome Bressler (Graves 1984, page S5499 of Congressional Record 1985a; Gordon 1987, page 497 of US Senate 1987; Farber 1989, page 110). -------------- On August 4, 1976, G.D. Searle representatives met with the FDA and convinced them to allow G.D. Searle to hire a private agency, University Associated for Education in Pathology (UAREP), and pay them $500,000 to "validate" the other 12 studies (Gordon 1987 page 498 of US Senate 1987) According the FDA Commissioner during the early 1980s, Arthur Hull Hayes, the UAREP investigation was to "make sure that the studies were actually conducted." As described by Florence Graves (1984, page S5500 of Congressional Record 1985a): "The pathologists were specifically told that they were not to make a judgment about aspartame's safety or to look at the designs of the tests. Why did the FDA choose to have pathologists conduct an investigation when even some FDA officials acknowledged at the time that UAREP had a limited task which would only partially shed light on the validity of Searle's testing? The answer is not clear. "Dr. Kenneth Endicott, Director of UAREP, said in an interview that the FDA had 'reasons to suspect' that Searle's tests 'were not entirely honest.' Because the FDA 'had doubts about [Searle's] veracity,' Edicott said, officials wanted UAREP 'to determine whether the reports were accurate.' "FDA scientist Dr. Adrian Gross, in a letter to an FDA official, said, 'speaking as a pathologist, it seemed questionable that the group could do the kind of comprehensive investigation that was required. He pointed in particular to a variety of issues that needed to be investigated. He said some of these would involved closely questioning administrators and lab technicians about their practices. Since many important issues that should be investigated 'have nothing to do with pathology,' he said, only trained FDA investigators were qualified to do a comprehensive evaluation of the testing. . . . "Meanwhile, an interview with Endicott indicates that Adrian Gross was right: the pathologists couldn't--and didn't--carry out a comprehensive review. . . . As former FDA Commissioner Alexander Schmidt put it in a recent interview, UAREP looked at the slides to determine whether they had been misrepresented, but didn't look at the conduct of the experiments in depth. The 1975 [FDA] task force investigation looked at the conduct of the experiments in depth, but did not look at the slides. . . . Endicott agreed . . . 'We could only look at what was there--the tissues.' The findings of this investigation where released in the Bessler Report in August 1977 (see below). 1977 ---- Donald Rumsfeld, who was a former member of the U.S. Congress and the Chief of Staff in the Gerald Ford Administration, was hired as G.D. Searle's President. Attorney James Turner, Esq. alledged that G.D. Searle hired Rumsfeld to handle the aspartame approval difficulties as a "legal problem rather than a scientific problem." (Gordon 1987, page 497 of US Senate 1987). As layed out by Mary Nash Stoddard (Stoddard 1995a, page 11), Rumsfeld hired: John Robson as Executive Vice President. He was a former lawyer with Sidley and Austin, Searle's Law Firm and also served as chairman of the Civil Aeronautics Board, which was then connect to the Department of Transportation. Robert Shapiro as General Counsel. He is now head of Searle's NutraSweet Division. He had been Robson's Special Assistant at the Department of Transportation. William Greener, Jr., as Chief Spokesman. He was a former spokesman in the [Gerald] Ford White House. Donald Rumsfeld is now on the Board of Directors of the Chicago Tribune which recently wrote a glowing article about the NutraSweet Company (Millman 1995, Mullarkey 1995). --------------