The Dangers of Aspartame and the Silence of Public Authorities
The wise man doesn’t give the right answers, he poses the right questions.
—Claude Lévi Strauss
“Those who attack the safety of aspartame are also attacking the independent determinations of the health and regulatory authorities of the world. The fact is, Senator, that every single authoritative scientific, medical and regulatory body in the United States and around the world that has ever examined the scientific evidence on the safety of aspartame has each, independently and separately, arrived at a single identical conclusion, and that is that aspartame is safe.”1 This strong statement made by Robert Shapiro is particularly intriguing given that aspartame owes its success worldwide to an (unsavory) “herding effect,” like the one that led village children to follow the Pied Piper.
In The World According to Monsanto, I talked at length about the path taken by the Saint Louis company’s ambitious and arrogant director, who wanted to revolutionize the world with genetically modified organisms (GMOs). He began his dazzling career as an attorney at Searle, and in 1983 he was named CEO of NutraSweet, the pharmaceutical company subsidiary tasked with producing aspartame (sold in the United States as “NutraSweet”). His role was further established in 1985 when Searle was bought by none other than Monsanto, whose leadership he would assume in 1995.2
1987: Revelations of the Metzenbaum U.S. Senate Commission
In November 1987, Robert Shapiro was called as a witness [see above statement] to a Senate hearing in Washington, DC, organized by Howard Metzenbaum—a democratic senator from Ohio who had always been openly opposed to aspartame. Aware that an outright ban on the artificial sweetener was out of reach, he fought instead for what he considered to be a measure of public hygiene: obligatory labels indicating the amount of aspartame contained in food products. He had already started down that line of questioning during a congressional session on May 5, 1985: “But with all the concerns raised about the safety of NutraSweet, does it not make sense, is it not logical, for individuals and their physicians to know how much NutraSweet is in the diet soda? What could be so terrible about stating the amount? How else will the user, or the physician, know if the person is exceeding reasonable consumption limits, particularly during the summer months?”3
I listened to the five-hour recording from the November 3, 1987, hearing, available on the cable television channel, C-Span.4 I have to say that I was fascinated by the Americans’ capacity to very officially reveal an entire series of highly disturbing facts, even if it ultimately changes nothing. Case in point: nearly a quarter of a century after the hearing, aspartame still has not been banned, or even investigated. I subsequently discovered that the Pentagon had placed the substance on a list of candidate products for the development of chemical weapons. And that no fewer than ten highly placed Food and Drug Administration (FDA) officials—who had worked under Arthur Hayes (the agency head from 1981 to 1983) to obtain approval for aspartame, initially for use in dry foods (1981) then in carbonated beverages (1983)—were all subsequently recruited by Searle or Monsanto. Including Michael Taylor.
In my investigation into Monsanto, I described how Taylor, a lawyer with a consulting firm working for the multinational company, was named to the number two FDA position in 1991 (where he would remain for three years) to direct the (non)regulation of GMOs, before becoming the vice president of Monsanto, the leading company in the field, in 1998. Considered an archetype of the practice of “revolving doors,” his oscillating career between the private and public sectors began in the early 1980s when he represented the FDA before a Public Board of Inquiry (PBI) on aspartame. As for Arthur Hayes, who left the agency in November 1983 once his term was completed, he became a consultant at Burson-Marsteller, one of the favored public relations firms of both NutraSweet and Monsanto.5
I also discovered that, at the request of Senator Metzenbaum, the Government Accountability Office—considered “the investigative arm of Congress”—had surveyed sixty-seven scientists: “more than half said they had some concerns over [aspartame’s] safety”; twelve said they had “major concerns.”6 I also found that, five years after going on the market, aspartame was the product that had generated the greatest number of spontaneous complaints to the FDA, 3,133 of which related to “neurological problems.”
Senator Metzenbaum invited Major Michael Collings to exemplify the (numerous) “side effects”—to which I will return—of the white powder that had “captured the tastebuds of the American consumer,” to borrow the senator’s expression. Collings, a U.S. Air Force pilot and experienced long-distance runner (“five-to-eight-mile jogs in Nevada’s desert heat”), had gotten into the habit of drinking “around a gallon [of Diet Coke and Kool-Aid] per day.” Gradually, he began to experience slight tremors in his arms and hands; then, on October 4, 1985, he lost consciousness and had an epileptic seizure. After a medical leave of absence, he set out for the Australian desert where he was deprived of his favorite beverage; his symptoms disappeared. Once home in the United States, he returned to his former habits. And the tremors returned, culminating once again in an epileptic seizure. A physician recommended that he avoid all products containing aspartame. Visibly moved, Collings explained that he had done so, and that all his symptoms had definitively disappeared. He added that ever since then, he hadn’t been able to fly, because the Air Force considered him disabled.7
Some would call this testimony anecdotal. But certainly not Dr. Richard Wurtman, a leading American neurology expert, who at the time was head of the Clinical Research Center at the renowned Massachusetts Institute of Technology (MIT). During his Senate hearing, he presented his study of two hundred aspartame consumers suffering from epileptic seizures, accompanied by frequent migraines and vertigo, despite having no previous history or detectable physiological cause.8 With the calm assurance of an implacable specialist, Wurtman explained that the source of the problems could be phenylalanine, an amino acid on which he had been working for fifteen years, and on which his lab had published over four hundred studies. Curtailing the (weak) arguments brought forth by NutraSweet’s representatives, who kept repeating that “the amino acid components of aspartame occur naturally in foods,” the neurologist affirmed that, on the contrary, consummation of aspartame has nothing to do with that of a normal protein, because phenylalanine is not consumed with other amino acids. That is why it has a far greater effect on blood plasma, which can affect neurotransmitter production and brain function.
“How many clinical studies have been made of NutraSweet, to your knowledge?” asked Senator Metzenbaum.
“On brain diseases? I’m not aware of any,” responded Wurtman without hesitation, before going to describe a number of extremely interesting facts.
The Maneuverings of the International Life Sciences Institute
In 1981, Wurtman testified before the PBI in favor of aspartame: the neurologist judged that when included in dry foods, the substance presented only minimal risks, as its consumption would remain limited. At the time, he was working as a consultant for the International Life Sciences Institute (ILSI).
In 1983, Wurtman learned that the company had requested that NutraSweet approval be extended to soda fabrication. He expressed his concerns to ILSI because, knowing Americans’ thirst for carbonated beverages, particularly among children, he feared that a massive influx of phenylalanine into the food chain would provoke serious health consequences. He therefore offered to lead a study to measure aspartame’s power to modify brain chemistry and favor the onset of epileptic seizures.9 Upon learning of his project, Gerald Gaull, Searle’s vice president, paid Wurtman a visit at his MIT lab and threatened to play the veto card at ILSI to have his funding cut. During his testimony, Wurtman explained that once he “became convinced [industry] was not really interested in exploring the toxicity of aspartame,” he decided to go without its financial aid.
Before quitting his “consultant” position, he wrote a letter to Robert Shapiro: “Dear Bob, I know you’ll agree that my value to Searle . . . derives in part from my telling the company some things that it would rather not hear . . . and then from helping the company to deal with those things. One such thing is that some consumers may develop significant medical symptoms after consuming very large amounts of aspartame, particularly if they happen, concurrently, to be on a low-calorie, low-protein, weight-reducing diet. . . . If Searle-supported studies are going to contribute to our understanding of these people and their symptoms, then the studies have to include them, and not be restricted to people who have a can or two of soda per day.”10 During the hearing, Wurtman stigmatized industry-supported studies that involved “giving a few doses, two or three doses, for one or two days.” “We see symptoms after people have taken the aspartame for weeks so one-day and two-day studies, as far as I am concerned, are of no value,” he noted. He then outlined the real problem, which is that there are no public funds to conduct serious studies, and mentioned several colleagues who had submitted projects and whom were told to ask the industry for help. Wurtman added that he continued his work by relying on his own laboratory’s funds.
Two other scientists questioned by the senators confirmed this warped system, which allows manufacturers to lock up research on their products. “The questions about phenylalanine effects on human brain function have not been asked,” said Louis Elsas, a geneticist at Emory University in Atlanta. “So we have spent millions of dollars through our current system on mostly irrelevant experiments without approaching those particular questions.” The pediatrics specialist and researcher was particularly concerned about the effects of amino acids on the fetus. “In the developing fetus such a rise in maternal blood phenylalanine could be magnified four- to six-fold by the concentrative efforts of the placenta and fetal blood brain barrier,”11 he explained. “The effect of such an increased fetal brain concentration would probably be [ . . . ] expressed as mental retardation, microcephaly, or potential certain birth defects.” He concluded that, through the same mechanism, irreversible brain damage could occur in babies from zero to twelve months old.
“Can you tell the Committee about your own experiences with the International Life Sciences Institute?” asked Senator Metzenbaum.
“Yes, sir. It was not good,” answered Elsas. “But I was asked after issuing concerns both privately and then publicly on ‘Nightline’ to give them a specific protocol for how I would approach these concerns. I did this [ . . . ] but without ever a written peer review of criticism. And the ideas are now reappearing three years later in other places funded by industry.”
William Pardridge, an endocrinologist and professor of medicine at the University of California Los Angeles, had a similar experience at ILSI.12 Focusing specifically on the blood–brain barrier transport of phenylalanine, he submitted two research projects on the effects of aspartame on children’s brains, both of which were turned down.
Confronted with these detailed accusations, ILSI’s representatives and collaborators made quite a poor showing. They included John Fernstrom, a psychiatrist at the University of Pittsburgh, who attempted to skirt the issue: “I can’t imagine a kid taking that ADI [for aspartame]. Fifty mg/kg is five cans of soda pop and [ . . . ] there is no way he is going to do that.” Then, he launched into a surrealistic discussion on the speed of aspartame breakdown, which is ostensibly “five times faster” in rats than in humans. Visibly exasperated, Senator Metzenbaum cut his stonewalling short by pulling out from behind his lectern—with a mischievous smile, one by one—several dozen common products that contain aspartame: carbonated beverages, chewing gum, cereals, yogurts, medications, vitamins, etc. The extremely theatrical accumulation of products elicited a volley of applause from the audience.
October 2009: The FDA Persists and Declares “the Substance Is Safe”
“I have no qualms in saying that if we are basing the amount of aspartame that we are putting in all these foods today on these [Searle] studies, then it is a disaster.” After the muddling of the ILSI scientists, Dr. Jacqueline Verrett’s testimony offered surprising clarity, provoking a religious silence in the hearing room. Verrett—appearing very severe in her square glasses and classic, tailored suit—had worked at the FDA as a biochemist and toxicologist from 1957 to 1979. In 1977, she joined Jerome Bressler’s team and therefore had access to the raw data for three infamous studies (one on DKP and two others on teratogenicity), which helped set the ADI for aspartame in the United States and Europe (see Chapter 14). With a deadpan tone, she referred to “animals returned to the study” after their tumors were removed, “animals [who] were recorded as dead, but subsequent records indicated the same animal was still alive,” and offered the cutting critique that “It is unthinkable that any reputable toxicologist giving a complete, objective evaluation of the data resulting from such a study could conclude anything other than that the study was uninterpretable and worthless and should be repeated.” She added, “In a quick scan of [the literature], I do not find studies that repeat any of this research enough to answer the questions that were raised. [ . . . ] and hence the acceptable daily intake figures remain in question and remain unanswered.”
Jacqueline Verrett (who passed away in 1997) co-authored an iconoclastic book in 1974—Eating May Be Hazardous to Your Health—in which she described her work at the FDA. Daring to challenge the famous agency’s reputation, she unabashedly writes: “Unfortunately, our food is not the safest in the world. [ . . . ] If some food additives were regulated as drugs they would be forbidden—except by prescription and then forced to carry warnings—especially to pregnant women.”13 She gives the example of Citrus Red 2, a food coloring that causes “stillbirths, fetal deaths and birth defects in animals.”14 The toxicologist also describes the role she played in banning cyclamate (E 952, which is still authorized in Europe). On October 1, 1969, she caused an upheaval by revealing the results of a study she had conducted on 13,000 chick embryos on television (on NBC). After being injected with cyclamate, the chicks were born with “severe birth defects” such as “deformed spines and feet, phocomelia.”15
Delving into hundreds of food additives authorized by the FDA, the majority of which “have never been tested,” she laments the fact that “All of us are involved in a gigantic experiment of which we shall never know the outcome—at least in our lifetime. How dangerous are the food chemicals we are eating? Are they contributing to cancer? To birth defects? To mutations? To liver, brain and heart damage and to a hundred other diseases? We don’t know. [ . . . ] We could at this moment be sowing seeds for a cancer epidemic in the 1980s or 1990s.”16
After reading this very disheartening book, I contacted the FDA in Washington, DC. It seemed like the perfect moment as President Barack Obama had just named Margaret Hamburg, a physician known for her commitment to community health (a domain largely overlooked by industry), to head the agency in March 2009. Familiar with the necessary procedure (thanks to my investigation into Monsanto), I contacted the press office where I encountered Mike Herndon, a civil servant who, after giving me the runaround, finally sent me the e-mail address of a key figure: James Maryanski, the former FDA biotechnology coordinator. From the way Herndon gently blew me off, it appeared that he had gotten wind of my film The World According to Monsanto, in which Maryanski proffered several sensational revelations on the links between the agency and the St. Louis-based company. I then had to write to Joshua Sharfstein, Margaret Hamburg’s right-hand man, who quickly intervened on my behalf (proof of a shift in attitudes in America). As a result, poor Mike Herndon found himself obligated to set up a meeting for me with David Hattan, the agency’s toxicologist responsible for overseeing food additives. When I entered the senior toxicologist’s office on October 19, 2009, I thought I was hallucinating: it was the same man who had sat beside Commissioner Frank Young during the infamous Senate hearing on November 3, 1987. It goes without saying that, at the time, Young had obstinately defended the approval of aspartame, under Hattan’s approving gaze.
“I saw you in C-Span’s archived footage,” I told him, slightly amused.
“Yes . . .”
“Jacqueline Verrett wrote this book here, maybe you know it, Eating May Be Hazardous to your Health. Have you read it?” I asked, holding the work out to the visibly tense toxicologist.
“Can you open it to page 96? I would like to have your comment, you have been working here for a long time—she says: ‘It’s not that government decision-makers are corrupt . . .’ That’s a good thing?” I interjected, scrutinizing David Hattan, who nodded in agreement with a frozen smile. I continued to read: “‘. . . but their sense of duty is constantly eroded by industry contacts and the consideration of short-term effects on industry instead of long-term effects on consumers.’ Do you think that’s accurate?”
“No, I don’t agree with her,” responded the toxicologist. “I don’t think that any of us in the FDA would feel we’re doing our job adequately and appropriately if we didn’t put consumer safety ahead of any kind of consideration of industry well-being. That’s turning the whole safety assessment paradigm on its head. No, I disagree with that completely.”
“You followed the approval process for aspartame very closely, correct? Since you arrived at the FDA when the PBI was being set up?”
“Yes.”
“The PBI, like other investigatory groups at the FDA, spoke out against authorizing the artificial sweetener. How do you explain that, several months later, the substance was nonetheless authorized, even though the general opinion within the agency was that the Searle studies were absolutely unreliable?”
“Oh! I would welcome individuals, maybe even challenge individuals, to come and look at the actual administrative records that the FDA has in its files about what the FDA did to resolve that controversy. It took many people and many months and millions of dollars being spent by the sponsor, Searle . . . We are not defending everything that was done. There were some mistakes made and some shortcuts to the way the studies were conducted . . . it actually was before ‘good laboratory practices’; the standard of performance of studies was not nearly as rigorous then as it is now . . . Basically, although there were problems with the conduct of some of these studies, none of those problems was serious enough to invalidate the studies’ results and none of them changed the studies’ results that indicated that the compound was safe.”17
Ninety-One Side Effects
“The FDA received thousands of complaints about the side effects of aspartame,” I continued, as David Hattan glanced repeatedly at Michael Herndon, the press office representative seated behind me. “I have here an internal, declassified document presenting ninety-one symptoms: ‘headache, dizziness, vomiting, nausea, abdominal cramps, change in vision, diarrhea, seizures, memory loss, rash, sleep problems, change in menstrual pattern, edema, chronic fatigue, shortness of breath . . .’” The document I handed to the toxicologist (to refresh his memory) made headlines in 1995. It was obtained by Betti Martini, the founder of “Mission Possible,” thanks to the Freedom of Information Act (see Chapter 14). It revealed that approximately 10,000 people spontaneously contacted the FDA to report problems they believed to be linked to aspartame.18 And according to a rule accepted by the agency, only 1 percent of consumers who encounter problems with a substance bother writing, which signifies that 1 million Americans could have suffered from the side effects of aspartame (between 1981 and 1995).
All the symptoms described in the FDA document mirrored those observed by Dr. Hyman Roberts during his long career. The Palm Beach physician, whom I met on October 24, 2009, fortuitously developed an interest in aspartame in 1984.19 That year, he saw a sixteen-year-old female patient named Tammie who had a seizure in his office. The concerned doctor ordered countless exams, none of which revealed the source of the neurological problems. He concluded that the only possible cause was aspartame contained in the “diet sodas” Tammie had begun to drink in order to limit her sugar intake. Four years later, Roberts published a study on 551 patients who had visited him for at least one of the problems described in the FDA document. “The causative role of aspartame-containing products is supported by (1) the relief of complaints shortly after avoiding such products, and (2) their occurrence within hours or days of reexposure, frequently inadvertent. . . . A brief trial of abstinence might avoid multiple consultations, costly tests, and hospitalization.”20 In 2001, Roberts published a 1,020-page book in which he presents the clinical history of 1,400 patients.21 He observed an addiction phenomenon, notably among heavy consumers of diet sodas (over two liters per day) or “sugarless” chewing gum (at least one pack a day), which causes cravings during withdrawal.
“Did you contact the FDA?” I asked.
“Of course, but the agency never responded!” replied Roberts. “The industry considers all these cases ‘anecdotal,’ even though hundreds of thousands of people are concerned.”
In a letter he sent to Senator Howard Metzenbaum shortly after the November 1987 hearing, neurologist John Olney ironically noted, “I doubt whether the thousands of lay citizens who have generated these complaints have thought it out ahead of time and conspired to make all of their complaints sound like their central nervous system is being affected.”22
“Are you familiar with Dr. Roberts’ work?” David Hattan raised his eyebrows at the question before, after some hesitation, responding: “In reality, the FDA and the Searle company conducted supplementary clinical studies in order to evaluate those effects, like headaches and seizures. All of that was carefully tested and the result was that, in a controlled environment where we know the exact dose used, the exact moment of ingestion and the individual who consumed it . . . well, we can’t reproduce those effects.”
“I don’t know which studies Mr. Hattan is talking about,” said Dr. Ralph Walton coldly, during our meeting in New York on October 30, 2009. “It would be great if he sent me his references, as it’s precisely because there are no serious studies investigating the neurological effects of aspartame on humans that I decided to conduct my own research.” Walton, who is a professor of clinical psychiatry at Northeastern Ohio Universities, also “stumbled onto aspartame by chance.” “In 1985, one of my patients whom I had been monitoring for twelve years for chronic depression began to have epileptic fits and develop manic episodes,” he told me. “It was even more odd since she had been doing well for years and her antidepressant treatment hadn’t changed. After ruling out bipolar disorder, I did some digging to understand what had changed in her life. And I discovered that she had begin drinking ‘Crystal Light’ products in order to lose weight and was consuming one to two liters of it a day. As soon as she stopped her intake, the problems definitively disappeared. I submitted a clinical report to a medical journal, and one of the reviewers was Richard Wurtman. He asked me if I knew of other similar cases. As I was head of the medical society in my city, I reached out to my colleagues, who reported dozens of cases. Ultimately, these clinical cases constituted a chapter in a book Dr. Wurtman published on the effects of phenylalanine on cerebral functions.”23
“Can you explain what kind of study you conducted?” I asked.
“In truth, if I had known the serious reactions that it was going to trigger, I never would have launched the experiment . . . We gave aspartame to volunteers for seven days, in a double-blind trial, meaning that the participants didn’t know whether they were receiving the substance or the placebo, nor did the researchers administering the products. A friend and colleague, who was forty years old and a doctor of psychology, experienced a retinal detachment and ocular bleeding and lost vision in one eye permanently. A nurse, who also volunteered, also presented ocular bleeding. The ethical committee supervising the study asked us to stop immediately. But, since thirteen people had followed the entire protocol, we were able to publish it with significant findings. Our conclusion was that people who had already experienced depressive episodes were extremely sensitive to aspartame.”24
“What dose did you use in your study?”
“Thirty mg/kg, since I wanted to remain below the ADI set by the FDA. That corresponds to about eight cans of Diet Coke a day, but it’s a dose that many people consume daily, since aspartame is found almost everywhere.”25
The Influence of Industry: The “Funding Effect”
On November 18, 1996, in Washington, DC, Ralph Walton, lawyer James Turner, Senator Howard Metzenbaum, and John Olney gave a press conference on an article they had just published: “The article we just published shows an increase of incidence of brain tumors and increased malignancies of brain tumors in human population in the USA, starting about three years after aspartame has been introduced.”26 Olney had reviewed data on brain tumors from the National Cancer Institute collected from 1970 to 1992 in thirteen geographic zones from the United States, which covered 10 percent of the American population. He found that an initial, localized increase in incidence “occurred in the mid l970’s and might be explained primarily by improved diagnostic methods.” It was followed by a “second phase [that] occurred abruptly in the mid l980’s, resulting in a 10 percent higher rate of brain tumors which has persisted to the present [through 1992].” He concluded that “the evidence presently available is not adequate to establish whether aspartame does or does not cause brain tumors. Therefore, new studies properly designed to answer this question are urgently needed.”
The publication drew a great deal of media attention, and the renowned current affairs show 60 Minutes decided to dedicate a special episode to aspartame. Lost amidst the massive amount of studies about the artificial sweetener, CBS producers asked Ralph Walton to conduct a systematic review of studies published in peer-reviewed scientific journals. An initial search in different databases, including MedLine, provided 527 references; the psychiatrist kept only those that were “clearly linked to the product’s safety for humans.”
“First,” Ralph Walton told me, “it’s important to note that the three fundamental Searle studies, which were used to calculate aspartame’s ADI, were never published! Furthermore, of the 166 studies that my team eventually selected, 74 were financed by the industry (Searle, Ajinomoto, or ILSI) and 92 by independent research bodies (universities or the FDA). One hundred percent of the industry-funded studies concluded that aspartame was safe. Of the 74, several had been published several times in different journals, under different names, but it was the same study. Of the 92 independent studies, 85 concluded that the sweetener posed one or more health problems. The remaining seven studies were conducted by the FDA and came to the same conclusions reached by those financed by the industry.”
“How can you explain such an incredible result?” I asked.
“Aha! Well, you know, money is very powerful . . .”
The blatant phenomenon Ralph Walton observed is known as the “funding effect.” David Michaels describes this worrying trend as follows: “When a scientist is hired by a firm with a financial interest in the outcome, the likelihood that the result of the study will be favorable to that firm is dramatically increased.” The new head of the Occupational Safety and Health Administration (OSHA) adds, “Having a financial stake in the outcome changes the way even the most respected scientists approach their research and interpret the results of experiments.”27
Paula Rochon, a Boston geriatrician, observed the funding effect when she was comparing clinical tests for nonsteroid, anti-inflammatory medications, such as aspirin, naproxen, or ibuprofen (Advil), used to treat arthritis. She showed that the industry-funded tests always presented favorable conclusions, even if careful review of the data did not confirm them.28 Four years later, a team led by the Canadian researcher Henry Thomas Stelfox at the University of Toronto made the same observations for calcium channel blockers—medications prescribed to treat hypertension and suspected of causing cardiac arrests. The researchers reviewed articles published between March 1995 and September 1996 and classified their authors in three groups according to their position in relation to the molecules: “favorable,” “neutral” and “critical.” The results: 96 percent of “favorable” scientists had a financial link with the calcium antagonists’ manufacturers, versus 60 percent of “neutral” authors and 37 percent of “critical” ones.29 Since then, the phenomenon has also been detected for oral anti-contraceptives, and drugs to treat schizophrenia, Alzheimer’s disease, and cancer.30
I carefully combed through Ralph Walton’s list of seventy-four studies financed by aspartame manufacturers, one of which caught my eye because it illustrates quite clearly the phenomenon of “black boxes” described by Bruno Latour in his book Science in Action. In order for a scientific statement to become an established fact whose origin cannot be reconstituted, it needs to be widely cited in multiple scientific articles. “A statement [is] fact or fiction not by itself but only by what the other sentences made of it later on,” explains the philosopher. “To survive or to be turned into fact, a statement needs the next generation of papers.”31 And that’s why Searle and company ensured the publication of several dozen “studies,” which never addressed the essential questions and whose goal was to dominate the scientific literature: a published study is a study that can be cited and thereby contribute to the transformation of a “fiction” to a “fact.” It is all the more effective if the industry can simultaneously block the production of independent studies that are quite rightly tackling the essential questions—a job ILSI has fulfilled perfectly.
We have seen the dubious conditions in which the ADI for aspartame was set in 1981. Ten years later, Searle asked two of its scientists, Harriett Butchko and Frank Kotsonis, to publish an article about the conception of the ADI, “using the widely used food additive aspartame” as an example.32 This was an astute move, since it allowed the report to immediately establish the ADI for aspartame as a “black box,” whereas, four years after the Senate hearing, it was still far from being unanimously accepted: “Aspartame has been assigned an ADI of 40 mg/kg/day by the World Health Organization and regulatory authorities in Europe and Canada, and of 50 mg/kg/day by the US Food and Drug Administration,” write the authors, who then pepper their article with multiple references (fifty), primarily to studies financed by Searle (though the funding source is not detailed), and including those led by Jack Filer (nine references) who, as we have seen, would become the ILSI director! Who is going to verify that these studies, whose authors claim they were used to set the ADI, all date after 1979? Or that a study by a key figure like Filer—one intended to confirm the innocuousness of aspartame—lasted six hours, during which eight “normal adults” (four men and four women) ingested 10 mg of aspartame every two hours?33
“The problem,” said Ralph Walton, “is that all these low-quality, even biased, studies are published in peer-reviewed scientific journals. We’re still waiting for the ‘radical reform’ called for by Richard Smith.” The director of the prestigious British Journal of Medicine caused a sensation by publicly recognizing the limits and weaknesses of the peer review system (see Chapter 9), though it is considered to be indispensable to scientific publications. “We know that it is expensive, slow, prone to bias, open to abuse, possibly anti-innovatory, and unable to detect fraud,” he wrote. “We also know that the published papers that emerge from the process are often grossly deficient.”34 In his editorial, which rubbed many the wrong way (namely manufacturers), Richard Smith described an experiment led by Fioda Godlee and two colleagues at the journal: they intentionally inserted eight errors into a study they were going to publish. They then sent the text to 420 potential reviewers, 221 (53 percent) of who responded: the average number of errors highlighted was two, not a single reviewer spotted more than five errors, and 16 percent spotted nothing.
The Ramazzini Institute: “The House and the Forum for Those Who Spend Their Lives in the Name of Truth”
“I’ve been fighting for twenty years to get the National Toxicology Program [NTP] to conduct a study on aspartame,” James Huff explained to me in 2009. Huff is the associate director for chemical carcinogenesis at the National Institute of Environmental Health Sciences (NIEHS) and leads the International Agency for Research on Cancer (IARC) Monographs Programme (see Chapter 10). “Unfortunately, the FDA has always opposed such a study by playing its veto card.”35
“How do you explain that?”
“I think that the agency is afraid that we will prove the sweetener is carcinogenic,”36 the scientist answered, before directing me to an article that appeared in November 1996, following the publication of John Olney’s study on the increase in brain tumors. It quoted James Huff, as well as David Rall, the former director of the NIEHS who oversaw the NTP for nineteen years (until his retirement in 1990): “It’s a wonderful way to ensure that it isn’t tested,” said Rall. “Discourage the testing group from testing it and then say it’s safe.”37
“And yet, I read that the NTP published the results of a study on aspartame in 2005,”38 I continued.
“That’s true,” replied James Huff, “but I was opposed to the study, as were several NIEHS colleagues. It was conducted on transgenic mice in which a gene was inserted that renders them more susceptible to cancer. It’s a new experimental model irrelevant to nongenotoxic, chemical products. Like aspartame, which is not genotoxic, meaning it doesn’t produce mutations.39 The results of this study—which cost a lot for nothing—were of course negative and made the industry very happy.40 I was disgusted, which is why I actively participated in designing studies led by the Ramazzini Institute that actually confirmed the carcinogenic potential of aspartame. In my opinion, they are the best studies thus far conducted on the substance.”
The Ramazzini Institute—named in honor of the “father of occupational medicine” (see Chapter 7)—was founded in 1987 by Italian oncologist Dr. Cesare Maltoni, whose work on vinyl chloride spread panic among European and American plastic manufacturers (see Chapter 11). Housed in a magnificent Renaissance-era Bentivoglio castle, twenty miles from Bologna, the environmental oncology center defines its research projects in collaboration with the Collegium Ramazzini, composed of 180 scientists from thirty-two countries. They include some of the scientists cited in this book, such as James Huff, Devra Davis, Peter Infante, Vincent Cogliano, Aaron Blair, and Lennart Hardell. Once a year, this exceptional group gathers in Carpi, the “master’s [Bernardino Ramazzini] birthplace.” In an article published in 2000, which is both a veritable declaration of faith and a testament, Cesare Maltoni (who died in 2001) described what makes this academic collegium so original and unique. “Our time is characterized by the enormous expansion and the primacy of industry and trade, at the expense of culture (including science) and humanism,” he wrote. “The primary and, too often, unique goal of industry and trade is profit. The strategy of industry and trade, in order to meet their objectives even when in conflict with culture and humanism, has been marked by the creation of an alternative pseudoscientific culture, whose major aim is to pollute truth instrumentally, by contrasting culture and science and by muffling the voice of humanists.”41 Cesare Maltoni added that the collegium’s raison d’être is “to be the house and the forum for those who spend their lives in the name of truth, and to give solidarity to those who, in pursuing the truth, are attacked and humiliated.”
Since its establishment, the institute has tested some two hundred chemical pollutants, such as benzene, vinyl chloride, formaldehyde, and numerous pesticides. These studies have often played a role in decreasing the exposure standards in use thanks to their irrefutable findings. Contrary to the large majority of industrial studies, institute analyses are conducted on megacohorts of thousands of subjects, which of course reinforces their statistical potential.42 During my visit on February 2, 2010, I was impressed by the laboratory’s breadth (thirty thousand square feet). Enormous circular facilities housed nine thousand rats exposed to different levels of electromagnetic waves for an experiment that Dr. Morando Soffritti, who succeeded Cesare Maltoni, described as “top secret” with a knowing smile. “The second characteristic of our institute,” he explained, “is that, contrary to the recommendations within the guide to ‘good laboratory practice,’ our experimental studies don’t last two years. Instead, we allow our animals to live until their natural deaths. In fact, 80 percent of malignant tumors detected in humans are found after the age of 60–65 years old. It’s therefore absurd to sacrifice experimental animals in the hundred and fourth week, which, when applied to the human species, corresponds to the age of retirement, when the frequency of cancers and neurodegenerative diseases is the highest.”43
“That’s the Ramazzini Institute’s greatest strength,” confirmed James Huff. “When you arbitrarily interrupt a study after two years, you risk missing the carcinogenic effects of a substance. And several examples prove it. Cadmium is a widely used metal, notably for the fabrication of PVC or chemical fertilizers, which IARC classified in group 1 [‘carcinogenic to humans’]. And yet, experimental studies showed zero effect. Until the day a researcher decided to let the rats die naturally: he observed that 75 percent developed lung cancer in the last quarter of their life. Likewise, the NTP studied toluene and found no effects after eighty months. On the other hand, the Ramazzini Institute observed several cancers that appeared after eighty months. All researchers should adopt the Ramazzini Institute’s study protocols, because the stakes are important: we always glorify extended life spans, but what’s so great about living ten or fifteen years longer, if it means living one’s retirement stricken by any number of diseases that could have been avoided if our exposure to chemical products was better controlled? That’s why the two aspartame studies conducted by the Ramazzini Institute are so troubling.”
“Aspartame Is a Multipotential Carcinogenic Agent”
More troubling still is the fact that the European Food Safety Authority (EFSA) and the FDA rejected those two studies, as did all the other national regulatory agencies, including, of course, the French Agency for Food, Environmental, and Occupational Health and Safety (Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail, ANSES). I must say that, even after reviewing the agencies’ arguments at length, I remain unconvinced.
The first study, published in 2006, was conducted on 1,800 rats that ingested daily doses of aspartame between 20 mg/kg and 100 mg/kg, from the age of eight weeks to their natural death. The results: a significant increase, correlated to the dose, in lymphoma, leukemia, and renal tumors among the females, and schwannomas (tumors of the cranial nerves) among the males. “Had we stopped the experiments at 110 weeks of age, we would most likely never have demonstrated the carcinogenicity [of aspartame],” write the study’s authors. “The results of this mega-experiment indicate that aspartame is a multipotential carcinogenic agent, even at a daily dose of 20 mg/kg body weight, much less than the current acceptable daily intake.”44
Curiously enough—given that the FDA generally contents itself with data summaries submitted by manufacturers—the agency insisted in this specific case on receiving the entirety of the Ramazzini Institute’s raw study data. At least, that is the official argument it kept brandishing, namely by David Hattan who repeated it without batting an eyelid: “We looked at a small subset of the data. To us, those changes looked like the kinds of changes that you see all the time, the sporadic changes that you see as a result of animal testing. We asked two or three times and each time they said it was the policy of their research institute not to share the primary data with outside parties.”
“Why did you refuse to communicate the study’s raw data?” I asked Morando Soffritti, the scientific director of the Ramazzini Institute.
“I’m surprised the FDA told you that,” he responded with his unfailing lopsided grin. “We’ve been in contact with the FDA since 2005 and we sent them all the data in our possession.”
Nevertheless, in an opinion published on April 20, 2007, the American agency affirmed that “study data [ . . . ] does not support the conclusion that aspartame is a carcinogen.”45 One year earlier, the EFSA had produced a similar opinion, after a long introduction in which it inevitably invokes the laboriously constructed “black box”: “Aspartame has undergone extensive testing in animals and studies in humans, including four animal carcinogenicity studies conducted during the 1970s and early 1980s. These studies, together with studies on genotoxicity, were evaluated by regulatory bodies worldwide and it was concluded that they did not show evidence of genotoxic or carcinogenic potential for aspartame.”46 Then, the European body addresses the Ramazzini Institute study, whose “flaws bring into question the validity of the findings. . . . The most plausible explanation of the findings in this study with respect to lymphomas/leukemias is that they have developed in a colony suffering from chronic respiratory disease.” The review concludes “that there was no need to revise [ . . . ] the previously established Acceptable Daily Intake (ADI) for aspartame, of 40 mg/kg body weight (bw).”
“Why did you reject this study?” I asked Hugues Kenigswald, the chief of the Food Additive and Nutrient Division at EFSA (whom we met in Chapter 14).
“First of all, so it’s quite clear—this study was absolutely not rejected. On the contrary, it was studied [sic] with the greatest attention. However, what became very clear is that there are a certain number, if not a whole host, of methodological flaws that emerged in this study.”
“For example?”
“In particular, the fact that some rats displayed respiratory pathologies.”
“What’s the relationship between having a respiratory disease and a lymphoma or leukemia?”
“A respiratory disease makes it so that it provokes . . . is the source of tumors and can therefore completely confuse the issue; that’s exactly what happened in this study.”
Once again, the EFSA’s argument amused Morando Soffritti, who, comfortably seated in his chair, replied: “We don’t agree, for a number of reasons. First of all, because the inflammatory processes we observed in our animals are very often reliant on the fact that we allow them to die naturally without arbitrarily cutting their lives short. And, like humans in the last phases of their lives, pulmonary and renal complications are very common. What’s more, it’s never been shown that pulmonary or renal infections that appear at the end of life are capable of causing tumors in such a short period.”
“Did the rats in the control group have the same inflammatory problems?”
“Of course. We observed them in both the treated and control groups. The only difference between the two groups was that the experimental groups had ingested aspartame and the control group hadn’t.”
In 2007, Morando Soffritti’s team published a second study, more worrying than the first. This time, four hundred pregnant rats were exposed to daily aspartame doses of 20 mg/kg and 100 mg/kg and their offspring were monitored until they died. “We observed that, when exposure began during fetal life, the risk of developing the tumors observed in the first study increased quite significantly,” commented Soffritti. “Add to that the appearance of breast tumors among the female offspring. We believe that these findings should push regulatory agencies to act as quickly as possible, because pregnant women and children are the most frequent consumers of aspartame.” In the publication, Soffritti and his colleagues underline that, “At their request, we provided each of these agencies with all available raw data related to the study.”47
And yet, David Hattan said precisely the opposite: “We didn’t review the second study done by the Ramazzini Institute because, unfortunately, we couldn’t reach an agreement to obtain the raw data,” said the FDA toxicologist.
“That’s not true,” Soffritti would later retort from his Bentivoglio lab.
“You’re saying David Hattan is lying?” I asked.
“You could say he’s lying.”
In its March 19, 2009, opinion, the EFSA underlines that “data were not provided by the authors,” which the Ramazzini Institute director fervently denies. Then, the European agency once again dismisses the leukemia and lymphomas observed, which it obstinately (and shockingly!) categorizes as “characteristic for chronic respiratory disease,” before proffering an explanation that outright stunned American scientists James Huff and Peter Infante, who found it “scabrous and unscientific”: “The increase in incidence of mammary carcinoma is not considered indicative of a carcinogenic potential of aspartame since the incidence of mammary tumors in female rats is rather high and varies considerably between carcinogenicity studies,” write the EFSA experts. “The Panel also noted that an increased incidence of mammary carcinomas was not reported in the previous ERF [European Ramazzini Foundation] study with aspartame which used much higher doses of the compound.”48
“It’s incredible that those experts could write that,” said James Huff. “It seems like they didn’t understand the originality of the study, which was to begin exposure in the womb. What’s troubling is precisely the fact that offspring developed breast tumors that the adult rats in the first study did not. We observe exactly the same phenomenon with endocrine disruptors: it’s the daughters exposed during fetal life who have breast cancers, not their mothers!”
The EFSA’s argument was clearly surprising, and yet it was the only one used by Hugues Kenigswald to justify the decision to ignore the Italian study’s results: “The breast tumors described in the second study didn’t appear in the first study,” he explained, while glancing at the two European civil servants sitting behind me. “Therefore the findings of the two studies are inconsistent.”
“How do you explain the EFSA’s argument?” I asked Morando Soffritti, who clearly weighed his words before responding.
“Evaluations done by experts from different agencies are often hasty and not entirely thought out,” he said. “If they had taken the time to measure the implications of exposure beginning in fetal life, they might not have made a judgment that was so trivial from a scientific point of view.” In the meantime, in an April 2009 statement, the International Sweeteners Association (ISA) welcomed the EFSA opinion, which “re-confirms the safety of the low-calorie sweetener aspartame, rejecting claims by the Ramazzini Institute (Italy) alleging that aspartame was unsafe. [ . . . ] These conclusions also support the previous EFSA opinion on aspartame issued in May 2006.” And finally, “These conclusions from EFSA are entirely consistent with the global scientific consensus.”49
Conflicts of Interest and a Pandora’s Box
I have already said this and I will repeat it again: the arguments proffered by the EFSA and FDA are entirely unconvincing. How, then, can we understand why these agencies chose to ignore two studies conducted by an institute regarded as a heavyweight in the field of environmental oncology, while they continue to defend tooth and nail the ADI for aspartame, which is based on studies that, to say the least, present serious “methodological flaws” (to borrow Hugues Kenigswald’s words)? Intrigued, I decided to identify the twenty-one experts in the EFSA’s Panel on Food Additives and Nutrient Sources Added to Food, known as the ANS panel.
Since 2002, the EFSA experts—who have permanent posts, unlike those at the Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Meeting on Pesticide Residues (JMPR) or the Joint FAO/WHO Expert Committee on Food Additives (JECFA)—have been obligated to declare their conflicts of interest, which can be consulted on the EFSA’s website. That’s where I discovered that John Christian Larsen, the panel president, works for ILSI! As do John Gilbert and Ivonne Rietjens, who also has financial ties to the Flavor and Extract Manufacturers Association (FEMA). Jürgen König has contracts with Dannon, a huge aspartame user. But the grand prize, if I may say so, goes to Dominique Parent-Massin, who sits on scientific committees at Ajinomoto, the Japanese aspartame giant, and Coca-Cola, a long-time user of sweeteners and founding member of ILSI! As director of the Food Toxicology Laboratory at Brest University (France), Parent-Massin even headed the food additives panel at the French Food Safety Agency (Agence Française de sécurité sanitaire des aliments, AFSSA [renamed ANSES in 2010])! The Japanese manufacturer’s French “dream team” is rounded out with France Bellisle, a researcher at the National Institute of Agronomic Research (Institut national de la recherche agronomique, INRA) who is a member of the scientific committee at the European Food Information Council (EUFIC)—which is financed by large food processing companies—and Bernard Guy-Grand, head of the Nutrition Department of Hôtel-Dieu Hospital (Paris) and president of Ajinomoto’s scientific committee. Note that Dominique Parent-Massin refrained from stating her affiliation when acting as a “health authority” during a hearing to defend aspartame’s safety.50 As such, during the 2006 Bichat conference, she adopted a familiar refrain: “Aspartame is one of the most extensively studied additives in the world.”51
I of course questioned Catherine Geslain-Lanéelle, the EFSA’s executive director, about the conflicts of interest held by certain members of the ANS panel, especially Dominique Parent-Massin. In all honesty, I was very curious to meet this ex-director of the Food Department of the French Agricultural Ministry (and a very zealous one at that), who (as we saw in Chapter 6) had refused to submit the Gaucho market authorization dossier to Judge Louis Ripoll. At the time, he was looking into the Food Department as part of an investigation on the insecticide’s toxicity in regards to bees. The very cordial executive director explained to me that the EFSA had begun to “reevaluate colorants” in 2008, and had recently decided to ban a “colorant used in Europe for thirty years in breakfast products and sausages consumed in Great Britain and Ireland.” “A review of the studies showed that it was genotoxic,” she continued, “so we took it off the market, just as we’ve done previously for certain artificial flavorings.”
“That’s certainly good news,” I said. “As for aspartame, I’m surprised to see someone like Dominique Parent-Massin, who has well-known ties with the principal aspartame manufacturer, on a food additives panel . . .”
“That means that when we conduct an evaluation of aspartame, that expert cannot be a rapporteur, cannot prepare the panel opinion, and cannot participate in deliberations on the subject, because he or she has a conflict of interest.”
“So for example, Dominique Parent-Massin didn’t participate in the aspartame opinion published in March 2009?”
“No . . . It’s important to understand that today public research is often linked to private research and, therefore, it’s impossible to find experts who have never had contact with industry—I don’t think they exist anymore,” Catherine Geslain-Lanéelle admitted. “That’s why we established a rule that scientists who have worked or are working directly for a product’s manufacturer are disqualified from participating in its evaluation, and that’s what happened with Dominique Parent-Massin.”52
But, in any case, transparency clearly has its limits. Dominique Parent-Massin’s declaration of conflicts of interest, which I found on the EFSA site before my visit to Parma, disappeared several days later! It was replaced by a new one that omitted any mention of the expert’s ties to Ajinomoto and Coca-Cola. The anecdote (once again) amused Morando Soffritti, who recounted his own: “A senior EFSA official told me once, ‘Dr. Soffritti, if we admit that the results of your studies are valid, we’ll have to ban aspartame first thing tomorrow. You have to realize that that is impossible.’”
Everything indicates that, even beyond its huge economic stakes, aspartame has become an unassailable fortress, as emphasized by Erik Millstone, the relentless thorn in the regulatory agencies’ collective side. “If they admit to making a mistake, that would provoke a loss of confidence. And also, they’re undoubtedly afraid that it would open the floodgates,” he explained with a very accusatory tone. “People might say: perhaps you haven’t made just one error, but many; or maybe the entire process is defective! Aspartame is a Pandora’s box—if it opens, the entire system could go up in smoke. That’s true for bisphenol A as well, another product that symbolizes the inefficiency of the regulatory system’s functioning over the past fifty years.”