UPI REPORT PART 2:
UPI Investigative Report: 10-07-87
Seizure, Blindness victims point to NutraSweet
By GREGORY GORDON
WASHINGTON (UPI) Susan Yarmey, a free-lance writer from Quincy,
Mass., awoke on a hot July morning in 1984 with a large bump on her head
and bruises all over her body.
"I had no recollection of what happened. There were marks on the wall,
two wooden steps were broken and there was a nice gash on the wall where
my head hit," she said.
Yarmeyís doctors diagnosed her injuries as resulting from a "classic"
epileptic seizure. She and Massachusetts Institute of Technology
neuroscientist Richard Wurtman believe the incident may be connected to
her consumption of the artificial sweetener, NutraSweet, know
generically as aspartame.
"A friend in New York directed me to the possible effects of NutraSweet
consumption...I was probably, at that particular time period, doing a
liter and a half to two liters (of diet soda with NutraSweet) a day,"
said Yarmey, who said when she stopped taking NutraSweet her problems
disappeared.
Yarmey is not alone. Many NutraSweet consumers, particularly heavy
users, who have suffered headaches, tremors, blindness, allergic
reactions and seizures, blame NutraSweet for their ailments.
Wurtman says he personally is aware of more than 200 cases in which he
suspects NutraSweet has caused health problems such as headaches,
dizziness, and seizures.
Wurtman says the problem might be solved simply by stiffening the
labeling requirements for NutraSweet products so that certain identified
groups can monitor their intake.
"The groups I would identify are pregnant ladies, small children, people
with a history of seizures and people who are taking certain drugs that
interact with phenylalanine," an amino acid in the sweetener, Wurtman
said.
Another former NutraSweet consumer, Shannon Roth, a mother of two who
works as a goldsmith in Ocala, Florida, organized Aspartame Victims and
Their Friends, Inc. after suffering blindness in one eye. She said the
group now has about 700 members.
"I got up in the morning and had two packs (of Equal, the NutraSweet
tabletop version) in each cup of coffee...three or four cups of coffee
before noon. Then I'd switch to the iced tea with it," Roth said.
In the summer of 1984, Roth said, she began to experience headaches,
sleep and memory loss, and irritability.
After getting out of bed one morning, she discovered she couldn't see
when she closed her right eye, Roth said. "I could see like through a
black veil. It was like a centralized, almond-shaped black spot," she
said.
Doctorsí laboratory tests failed to trace the cause of her partial
blindness, she said, and one doctor told her not to expect vision to
return to her eye.
Roth said she suspected NutraSweet as the cause after learning of a
similar case that was allegedly linked to the sweetener, and after about
four weeks without NutraSweet, her headaches and other problems ceased.
Her sight began to return a few weeks later, she said.
Joyce Wilson, a real estate agent in Stockbridge, Georgia, said she
began suffering from high blood pressure, dizziness and other ill
effects in 1982 after using Equal in her coffee and eating NutraSweet-
flavored puddings. She said that in 1984 and 1985, she lost some vision.
"I'm not blaming this all on NutraSweet," Wilson said. "I'm just saying
itís a strange coincidence that when I started using it, I started
falling apart."
Dr. Morgan Raiford, an ophthalmologist at Emory University examined
both Roth and Wilson and believes their problems stem from consumption
of the methyl alcohol in NutraSweet.
Dorris Bookhart, 43, a legal secretary in Lodge, S. Carolina, started
having what were later diagnosed as temporal lobe seizures in August of
1984. At the time, she said, she was drinking four 16-ounce bottles of
Diet Coke a day, as well as diet lemonade. Both contained NutraSweet.
In January of 1985, after six months of problems, she suffered a grand
mal seizure, a convulsive episode in which the victim loses
consciousness, she said. Her doctors were mystified by the seizures, but
they ruled out epilepsy, Bookhart said.
She said she suspected NutraSweet as the culprit when, at her husbandís
suggestion, she stopped drinking Diet Coke and the problems ended.
"I've cried a lot of times thinking these people have destroyed my life
and there isn't a damn thing I can do," she said.
Another heavy user of the artificial sweetener, Larry Taylor of
Arlington, Texas, said he was hospitalized for five or six days to
undergo a battery of tests after suffering a grand mal seizure in 1985.
He was also a victim of migraine headaches that became more frequent
between 1982 and 1984. After his seizures, Taylor, an anesthetist, was
not allowed to work until January of this year (1987), a disability he
said left him "financially devastated."
---------
What critics say about NutraSweet
By GREGORY GORDON =
WASHINGTON (UPI) ≠ Despite the NutraSweet Co.ís insistence that scores
of company studies have "proved" the sweetener is harmless, hereís a
sampling of concerns from a hard core of scientific critics:
What the critics say about NutraSweet
Dr. Rueben Matalon of the University of Illinois has reported that
heavy consumption of NutraSweetís main component ≠ the amino acid
phenylalanine ≠ may cause neurological problems such as loss of memory
and concentration. Matalon and Dr. Louis Elsas of Emory University say
they fear aspartame consumption by some pregnant women can cause
irreversible brain damage in fetuses. They worry most about women among
an estimated 4 million to 20 million Americans who are carriers of the
genetic disease, phenylketonuria ≠ characterized by the liverís
inability to process phenylalanine. While there are an estimated 20,000
to 30,000 PKU victims nationwide who are warned not to take NutraSweet,
carriers or heterozygotes, do not have the disease and generally are
unaware of their sensitivity, they said. The company has said that the
Food and Drug Administration concluded, "NutraSweet did not present any
additional health risk to pregnant women."
Dr. Paul Spiers, a clinical neuropsychologist at Bostonís Beth Israel
Hospital, found in a recent pilot study that, after consuming
NutraSweet, some subjects with no previous problems failed to show the
usual improvement in performance on cognitive tests. He plans further
research. But Dr, Harris Lieberman of the Massachusetts Institute of
Technology, who has received industry funding for NutraSweet research in
the past, said his study of 20 adult males indicates that aspartame "has
no measurable effect on mood and performance in normal humans."
In St. Louis, Washington University allergist, Dr. Anthony Kulczycki
found that two women given NutraSweet capsules and a placebo suffered
allergic reactions to NutraSweet. The women reported hives and other
skin reactions after using the sweetener.
Dr. Donald Johns, a neurology resident at Massachusetts General
Hospital, reported last year that a "double-blind" study of a woman
suffering migraine headaches showed her problems were aggravated by
consumption of NutraSweet. NutraSweet, known generically as aspartame,
consists of phenylalanine and another amino acid, aspartic acid, linked
to a small quantity of methyl alcohol. Scientific critics seem to worry
most about phenyalanine.
Dr. Richard Wurtman, Massachusetts Institute of Technology
neuroscientist, says heavy NutraSweet consumption may so flood the
bloodstream with phenyalanine that other essential amino acids are
blocked from reaching the brain, causing chemical changes that can
affect behavior and lower the threshold at which many suffer epileptic
seizures. Wurtman and Dr. Donald Schomer of Harvard University are
testing seizure victims who used NutraSweet, particularly some whose
bodies may have trouble processing phenylalanine. The NutraSweet Co.
concedes aspartame raises phenylalanine levels, but says no harm
results, and that consuming the amino acids in NutraSweet "is just like
eating other foods containing the same protein components."
Another Wurtmen protege, Dr. Timothy Maher of Massachusetts General
Hospital, supported his mentor by reporting that mice, given a seizure
inducing drug and NutraSweet, suffered more seizures than those
receiving the drug alone. Dr. Henry Haigler, a scientist in a NutraSweet
Co. sister firm, said his similar study showed "no effect on seizure
thresholds."
Dr. William Pardridge of the UCLA Medical School, who also has done
phenylalanine research, said he most fears the sweetenerís effect on
children, who, he says, "are more likely to approach the FDAís
acceptable daily intake level of 50 milligrams per kilogram of body
weight. If youíre a child, seven to twelve years of age, the chances are
good you'll have five servings a day" ≠ close to the acceptable level,
he said. But Dr. Harvey Levy, head of the PKU clinic at Bostonís
Childrenís Hospital, wrote the Journal of the American Medical
Association that Pardridge made an "inaccurate interpretation" of their
data in predicting brain damage effects on fetuses from aspartame. Any
danger level, they said, "would seem to be considerably higher" than
levels from NutraSweet consumption.
Dr. Woodrow Monte, an Arizona State University food scientist, and Dr.
Morgan Raiford, an ophthalmology professor at Emory, worry that a
NutraSweet breakdown product, methyl alcohol, could produce severe eye
damage. Last year, Raiford examined more than a half dozen persons who
said they suffered eye problems after consuming NutraSweet heavily. He
said he diagnosed some cases of optic nerve damage and suspects
NutraSweetís methyl alcohol is the culprit. The company denies any
connection between NutraSweet and eye problems and has offered exams to
consumers who complain of such problems.
Dr. Sidney Wolfe, executive director of the Washington-based Health
Research Group, said, "The thing thatís really worrisome is that it
clearly affects brain metabolism in animals, and anyone who disputes
that is irresponsible."
Dr. John Olney of Washington University expresses fears about brain
tumors ≠ a problem he and other scientists say would not show up in
humans for 20 years and would be difficult to trace to NutraSweet. Olney
said Searle rat studies have shown conflicting brain tumor data. As
early as 1971, Olney reported that aspartic acid in aspartame killed
cells in the brainís hypothalamus region, which regulates glandular and
hormonal functions.
----------
The NutraSweet Company responds to UPI series.
WASHINGTON (UPI) ≠ In response to the United Press International series
of articles on NutraSweet, The NutraSweet Co. issued the following
statement:
A series of articles to be released this week by UPI seriously
misrepresents the vast body of scientific evidence, which establishes
the safety of aspartame.
Contrary to the impression created by these articles, the scientific
record has been carefully reviewed by independent and official
scientific and regulatory agencies around the world.
Without exception, each of these agencies has concluded that aspartame
is a safe sweetener which can be used as a normal part of the daily
diet. The following quotations are representative of expert scientific
and medical opinion around the world.
U.S. Food and Drug Administration: "The data and information supporting
the safety of aspartame are extensive. It is likely that no food product
has ever been so closely examined for safety...Few compounds have
withstood such detailed testing and repeated close scrutiny, and the
process through which aspartame has gone should provide the public with
additional confidence of its safety."
American Medical Association Council on Scientific Affairs:
"Consumption of aspartame of normal humans is safe..."
American Diabetes Association: "Aspartame has been determined to be
safe for the general population as well as for people with diabetes."
Government of Canada (Health Protection Branch): "Aspartame is one of
the most extensively studied chemicals permitted for use in food...Based
on the available data it has been concluded that aspartame would not
pose a hazard to health when used in accordance with the current
provisions of the Canadian food and drug regulations."
Government of Denmark (Danish Food Institute): "Research published in
the scientific literature and/or studied in detail by governments and
independent scientific committees maintains that the use of aspartame as
an additive does not bear any health risk at all...There is, therefore,
no toxicological basis for believing the intake of aspartame is soft
drinks and food products should give rise to harmful effects in children
or adults, even people with high level usage."
Government of Great Britain (UK Committee on Toxicity of Chemicals and
Food): "Following detailed consideration of all toxicological data, we
see no objection to the use of aspartame in food."
Other scientific agencies that have reviewed the evidence and confirmed
the safety of aspartame include the World health Organization of the
United Nations; the Scientific Committee on Foods of the European Common
Market; the Epilepsy Institute; and the American Academy of Pediatrics.
Aspartame has been reviewed and approved as a safe sweetener by the
official food regulatory authorities in all the leading nations of the
world, including many which forbid or restrict the usage of other
sweeteners.
A recent article by Harvard Medical School Prof. Peter Dews reviewed
the "massive evidence" that establishes the safety of aspartame. Dr.
Dews concluded: "Many articles of everyday consumption that are known to
be safe might not survive the scrutiny of such intensive and continued
investigation."
The respected consumer publication Consumer Reports summarized its
conclusions this way: "An objective weighing of the evidence suggests
that aspartame is the artificial sweetener to be preferred on safety
grounds."
The UPI articles also seek to discredit the process by which aspartame
was reviewed and approved by the FDA.
These charges have been conclusively rebutted by both the FDA, itself,
and by the General Accounting Office, the investigative agency of the
Congress. A full GAO report on the approval process concluded that the
FDA had properly followed the appropriate procedures and had adequately
addressed the scientific issues.
The UPI series is replete with misstatements and distortions, which
convey a totally misleading impression of the scientific facts. Any
concern or anxiety by consumers who read these articles is absolutely
unwarranted. Aspartame is safe as approved by FDA and regulatory
authorities around the world. Any contrary impression created by UPI
articles is a serious disservice to the public.
PART 2:
(Editorís Note: UPI investigative reporter Gregory Gordon spent eight
months examining industry research into the popular artificial sweetener
NutraSweet and the Food and Drug Administrationís handling of the
product permeating the diet food and drink markets. here is the second
in his three-part series.)
PART 2: NUTRASWEET APPROVAL MARRED BY CONTROVERSY
by: Gregory Gordon
WASHINGTON (UPI) Pouring over laboratory rat studies in the spring of
1981 in the governmentís final safety review of a new artificial
sweetener, senior statistician Satya Dubey of the Food and Drug
Administration was troubled.
Dubey, a member of a special FDA "commissionerís team" formed to help
decide the fate of the product to be known as NutraSweet, wrote an
internal memo that brain tumor data from the rat tests was so
"worrisome" that he could not recommend approval.
Two other statisticians on the six-member team agreed with Dubey that
the Chicago-based G.D. Searle Co. had not proved with "reasonable
certainty" the safety of the sweetener, known generically as aspartame.
A 1980 Public Board of Inquiry had voted 3-0 to ban aspartame because of
similar fears.
But a few weeks later on July 18, 1981, new FDA Commissioner Arthur
Hull Hayes, Jr., a pharmacologist who had been in office less than three
months and had little background in food additives, overturned the board
and approved the use of aspartame in dry foods.
The ruling, one of the first regulatory actions of the Reagan
presidency, came at a time of growing concern that the most widely used
low-calorie sweetener, saccharin, was linked to cancer. Thus Hayesí
approval of NutraSweet profoundly changed the eating habits of millions
of Americans, handing Searle a financial bonanza.
It also climaxed a topsy-turvy, eight year FDA review process in which
the agency approved the sweetener, then banned it and demanded a grand
jury investigation of its manufacturer, only to reverse course again
after reexamining the issue at least five times.
Now, six years after Hayesí ruling, its uses expanded, the sweetener is
widely consumed in diet sodas, puddings, cereal, drink mixes, and even
chewing gum and vitamins. Yet NutraSweet and its FDA approval remain at
the center of controversy, the sweetenerís safety questioned by a small
corps of independent scientists; defended by its manufacturer and the
diet food and drink industry.
In a recently released report, the General Accounting Office concluded
that the FDA "adequately followed" its food additive approval process on
NutraSweet.
Congressís investigative arm did not evaluate the sweetenerís safety. A
federal appeals court also has rejected court suits by consumer groups
challenging the NutraSweet approval.
United Press International has learned that more than 10 federal
officials involved with the NutraSweet review have taken private sector
jobs linked to the industry ≠ among them, Hayes, an acting FFDA
commissioner and former chiefs and acting chiefs of the agencyís Bureau
of Foods.
In addition, many of the scientists who have produced favorable studies
or served as outspoken advocates of NutraSweetís safety have received
grants or consulting fees from Searle and the industry.
Consumer lawyer, James Turner, who has unsuccessfully pressed petitions
for a NutraSweet ban as part of an 11 - year campaign against the
sweetener, asserted, " NutraSweet is an opportunity for the entire
country to look in great detail at how we make food safety decisions. It
is a rickety, 19th Century process."
G.D. Searle began to study the artificial sweetener aspartame soon
after a company laboratory chemist, James Schlatter, stumbled on the
compound when he licked it off his finger while conducting ulcer
research in 1965.
In a memo on Dec. 28, 1970, a Searle official laid out a plan for
winning FDA approval for the sweetener. " We must create an affirmative
atmosphere in our dealing with them," Herbert Helling wrote senior
company executives. Helling suggested that Searle representatives
carefully order proposals to the FDA to put Bureau of Foods officials
"into a yes saying habit." If FDA officials could be swayed to do Searle
some favor, he asserted, it would "help bring them into a subconscious
spirit of participation."
On July 26, 1974, just 15 months after Searle petitioned for approval,
FDA commissioner Alexander Schmidt approved aspartame use in dry foods,
allowing a 30-day period for public hearings and comment. He acted on a
strong endorsement from the Bureau of Foods, now called the Center for
Food Safety and Applied Nutrition (CFSAN).
At that point, consumer attorney Turner, author of a 1970 book about
food additives, objected to the short comment period. Turner was joined
in his protest by a now-defunct public interest group and by Dr. John
Olney, a Washington University neuropathologist who had linked aspartame
to brain lesions in mice.
Schmidt promptly froze the approval. In an action that was the first of
its kind, he ordered that a Public Board of Inquiry be named to look
into aspartame.
Schmidt also had been alerted to conflicts between Searle research
reports and conclusions from independent animal studies that the firmís
anti-infective drug, Flagyl and its cardiovascular drug Aldactone may
cause cancer. He named a Bureau of Drugs task force to investigate.
Philip Brodsky, the unitís since-retired lead investigator, said
aspartame was included in a broad inquiry into Searle animal studies on
five drugs and the Copper-7 intrauterine device to surprise the company.
"We didnít think theyíd expect us to cover it."
The task force assailed Searleís conduct of research on most of the
products, including aspartame, in a searing, 84-page report.
"At the heart of the FDAís regulatory process," the report said, "is
its ability to rely upon the integrity of the basic safety data
submitted by sponsors of regulated products. Our investigation clearly
demonstrates that, in the G.D. Searle Co., we have no basis for such
reliance now."
The task force charged, for example, that the company removed tumors
from live animals and stored animal tissues in formaldahyde for so long
that they deteriorated. Instead of performing autopsies on rhesus
monkeys that suffered seizures after being fed aspartame, the company
had financed a new monkey study with a different methodology that showed
no problems.
For the next seven years, Searleís petition was tied up in reviews by
the task force and other sharply critical FDA panels. At the task
forceís request, Richard Merrill, the FDAís general counsel, demanded in
a letter that Samuel Skinner, the U.S. attorney in Chicago, open a grand
jury investigation of Searle and three of its employees.
One Searle official named by Merrill was Robert McConnell, who had been
director of Searleís Department of Pathology and Toxicology and oversaw
most of the companyís aspartame research.
McConnellís Detroit lawyer, Gerald Wahl, said that as the inquiries
heated up, his client was suddenly awarded a $15,000. bonus and asked to
take a three-year sabbatical by director Wesley Dixon. Wahl said Dixon
told McConnell he had become a "political liability," a remark Dixon
later denied making.
McConnell received his annual salary of more than $60,000 during the
sabbatical at the Massachusetts Institute of Technology, but he never
got his job back, and ended up suing the company, Wahl said.
"I've represented hundreds of executives, but I've never seen anybody
get the deal that McConnell got," he said. "When you boil it all down,
they were looking for continued support from McConnell during the
inquiries."
Wahl said McConnell had felt pressure to hurry his research because of
the "profit motive," but the company never ordered him to alter test
results.
Chief investigator Brodsky said that "politicized" handling of the task
force disclosures, at hearings chaired by Sen. Edward Kennedy D-Mass.,
was one reason he retired in 1977. He said the main witnesses, Searle
executives, and top FDA officials uninvolved in the investigation gave
"the wrong answers to the wrong questions"ÖThey didnít even let the
experts answer the questions.
The FDA, rocked by controversy, established a set of "good laboratory
practices" ≠ minimum standards for future corporate research work.
Richard Ronk, deputy Bureau of Foods chief, stressed that Searle
practices were typical of the industry at the time, "not the worst on
the block."
Searleís fortune did not begin to change until 1977, when Donald
Rumsfeld, White House Chief of Staff under Gerald Ford, was named its
new president.
Turner alleged that Searle chose, with Rumsfeldís hiring, not to redo
the questioned studies on belief he could handle aspartame as "a legal
problem rather than a scientific problem."
The company also hired another Ford White House official, William
Timmons, as a Washington lobbyist.
Before deciding on Merrillís grand jury request, U.S. Attorney Skinner
and an aid agreed in February 1977 to meet with lawyers for Searle,
including Newton Minow, a partner in the law firm of Sidley & Austin.
A month later, Skinner, a Republican appointee who was looking for a
job as a result of Jimmy Carterís election, informed aids in a memo that
he had begun preliminary employment discussions with the law firm.
Withdrawing from the Searle matter, Skinner suggested his designated
successor, Thomas Sullivan, be left to decide whether to open a grand
jury inquiry-a move that delayed action for at least four months.
Sullivan took office just 12 weeks before expiration of the statute of
limitations for prosecuting alleged false statements on aspartame. While
the grand jury inquiry ultimately was convened, those allegations were
not explored.
Skinner denies any conflict of interest.
Assistant U.S. Attorney William Conlon worked with the grand jury until
October 12, 1977, two days after the statute of limitations expired on
the aspartame allegations. No indictments were brought on the few
matters investigated. Conlon, who declined comment, joined Sidley &
Austin 15 months later.
Following issuance of the task force report back in March 1976 and
facing a dilemma as to how to proceed, the FDA sought new reviews of
several "pivotal" studies ≠ long term animal tests to see whether
aspartame causes cancer.
A new five-member internal FDA task force analyzed three of these
studies, and Universities Associated for Research and Education in
Pathology, Inc., a consortium formed by 15 universities, was contracted
to look at another dozen.
Much like the earlier team, the five-member FDA task force, headed by
veteran Chicago inspector Jerome Bressler, assailed the quality of
animal tests into whether the substance might cause birth defects and
tumors.
The report said Searle laboratory employee Raymond Schroeder, who
worked on related research, first told investigators the feed in the
study of the aspartame breakdown product DKP (diketopiperazine) was so
inadequately mixed it appeared the rats could "discriminate" and avoid
eating the DKP.
Schroeder, who has worked for another company since 1975, later backed
off his statement. He told UPI, "I just didn't feel qualified to speak
on something I didn't work onÖThereís no one twisting my arm."
Bressler criticized the companyís "sloppiness" on all three studies.
"The question you've got to ask yourself," he said in an interview, "is:
Because of the importance of this study, why wasn't greater care taken ?
The study is highly questionable because of our findings. Why didn't
Searle, with their scientists, not closely evaluate this, knowing fully
well that the whole society, from the youngest to the elderly, from the
sick to the unsickÖwill have access to this product?"
Howard Roberts, acting director of FDAís Bureau of Foods, appointed a
five-person task force to review the Bressler teamís findings pending a
decision on whether to throw out the three tumor and birth-defect
studies.
Jacqueline Verrett, a senior scientist on the review team, said members
were barred from stating opinions about the research quality. "It was
pretty obvious that somewhere along that line they (bureau officials)
were working up to a whitewash," she said. "I seriously thought of just
walking off of that task force."
Verrett, now a private consultant, said that she and other members
wanted to "just come out and say that this whole experiment was a
disaster and should be disregarded."
But on September 28, 1977, the panel reported that deviations between
Searleís raw data and its FDA submissions were "not of such magnitude as
to alter its conclusion."
Verrett said the bureauís intent seemed to be "to tone down what was
really found." She noted the bureau felt pressure because safety
concerns also had been raised about cyclamate, another alternative for
the cancer-linked sugar substitute, saccharin.
In October, 1978, a year after ordering the review that helped get
Searleís petition back on track, Robertís (acting Director of Bureau of
Foods) quit to become vice president at the National Soft Drink
Association. The NSDAís members later marketed a stream of NutraSweet-
flavored diet soft drink products.
Reached at NSDA, Roberts dismissed Verrettís criticism, asserting the
task force report "really was of no importance." He said he had no
concerns about the appearance of his taking the NSDA job, stressing he
does not represent NSDA before the FDA. "I sleep well at night," he
said.
Negotiations for an additional, outside review of Searleís studies had
begun with an August 4, 1976 meeting between Searle and 10 FDA
officials. During the meeting, Searle officials said they desired to
help pick the consultant to perform the review, and internal FDA memo
said.
Agency memos show the FDA soon was negotiating with the Universities
Association for Research and Education in Pathology for a half-million
dollar, company-funded "validation" of a dozen Searle studies.
The pathology organizationís review concluded that Searleís studies
were authentic and the discrepancies largely inconsequential.
Adrian Gross, an investigative consultant to the 1975 task force, later
said the 16-month review was "at best, irrelevant" because the group was
limited to analyzing "whether Searle lied about the data in its tests".
"It was not our task to challenge the validity of the experimental
methods, since the FDA had itself already accepted the methodology", the
groupís executive director, Kenneth Endicott, said.
Jere Goyan, who was FDA Commissioner in 1980, said he would have put
less weight on the review than on the findings of FDAís task forces.
Goyan also suggested that, after approving aspartame in 1974, the FDAís
Bureau of Foods may have "felt they had to keep their previous
position."
Regardless, the pathology groups findings carried major weight in the
final approval decision. The chairman of the 1980 Public Board of
Inquiry, Dr. Walle Nauta of the Massachusetts Institute of Technology,
said the board had to rely on those findings because it was denied
access to the task force reports by FDA officials.
"There was absolutely no way in which we could decide who was right
here," Nauta said. "We simply had to accept the data as they stood."
Nauta was joined on the panel by Drs. Vernon Young of MIT and Peter
Lampert of the University of California at San Diego.
Before voting 3-0 to ban NutraSweet on the narrow cancer issue, the
board itself was drawn into allegations of bias because two of the three
members came from MIT ≠ as did Bureau of Foods Chief Miller and several
scientists involved in the controversy.
Between 1979 and 1982, four more FDA officials who participated in the
approval process took jobs linked to the NutraSweet industry: Pape;
acting FDA commissioner Sherwin Gardner; Albert Kolbye, who was
associate director of the Bureau of Foods for toxicology, and Mike
Taylor, an FDA lawyer who represented the bureau before the Board of
Inquiry. All four denied any conflict of interest.
After the Board of Inquiry ruled against NutraSweet on Sept. 30, 1980,
Searle waited until January 21, 1981, the day after President Reaganís
inauguration, to press for a reversal of the FDA commissioner ≠ assuring
the new administration would decide the issue.
Jere Goyan, Hayesí predecessor as commissioner, said he found the delay
curious because, after eight years of legal battles, financially
struggling Searle "obviously was most anxious to have this thing
approved."
Robert Dormer, a lawyer for the NutraSweet Co., said there was nothing
special about the Jan. 21 date or the papers filed that day.
But with Reaganís election, it was virtually assured that a republican-
appointed commissioner would replace Goyan and decide the appeal- and
Searle had strong GOP connections with Rumsfeld at the helm.
Goyan had set up a five-member "commissionerís team" of scientists with
no prior involvement in the issue to review the boardís ruling.
On May 10 and 13, 1981, a month after Hayes took office, scientists
Satya Dubey, Douglas park, and Robert Condon each laid out concerns
about the sweetenerís safety in memos to team lawyer Joseph Levitt.
Dubey not only expressed reservations about reported incidence of brain
tumors in one key Searle rat study, but also said key data in another
study appeared to have been altered. Dubey, who still works at FDA,
refuses to discuss the matter.
Condon, another statistician on the team, and Park, staff science
advisor in the agencyís Office of Health Affairs, each said the
available evidence failed to prove NutraSweetís safety or lack of
safety.
Park said that Levitt hurried the panel to decide the issue. "They
wanted to have the results yesterday," he said. "We really didnít have
time to do the in-depth review we wanted to do."
Park said Levitt met frequently with Hayes and "was obviously getting
the pressure to get a resolution and a decision made."
Sources have said the office of Sen. Howard Metzenbaum, D-Ohio, has
received allegations of political influence in Hayesí final decision-
making process.
In a letter written after the FDA cleared NutraSweet, one former Searle
saleswoman, Patty Wood-Allott, asserted the Rumsfeld told his sales
force shortly after Reagan took office that if necessary, "he would call
in his markers and that no matter what, he would see to it that
aspartame would be approved that year." Rumsfeld declined to return
phone calls.
With three of five scientists on the commissionerís team opposing
approval, it was decided to bring in a toxicologist for his opinion on
isolated issues.
Goyan said if the decision were his, he never would have enlarged the
team. While the panel did not vote, it ended up split 3-3.
Levitt, who normally would have been expected to draft an options paper
spelling out scientific evidence on key issues, took an unusual tact. He
circulated an approval recommendation ≠ and only backed off when Dubey,
Park and Condon objected, team members said.
Levitt said he was not directed to draft the approval memo, but did so
as a "tactical" step to break the teamís week-long impasse by forcing
each scientist to state his views.
"It worked didnít it?" said Levitt, who later was promoted to a post as
an executive assistant to the FDA commissioner.
One team member said that during discussions, Hayes, appeared to be
abandoning the agencyís traditional standard of "reasonable" proof of
safety and looking for "proof of hazard."
Hayesí July 1981 approval decision came in the face of a Searle threat
to file a suit challenging the regulatory delays.
His ruling relied in part on a late rat study of brain tumors submitted
by Ajinmoto, a Japanese company that manufactures aspartame for Searle.
That study, however, tested Wistar rats, a strain that some scientists
said is more tumor resistant than the Sprague-Dawley rats used in
earlier research.
In his decision, Hayes wrote: "Few compounds have withstood such
detailed testing and the repeated close scrutiny and the process through
which aspartame has gone should provide the public with confidence of
its safety."
In late 1982, Searle petitioned for FDA approval to use the sweetener
in diet soft drinks and childrenís vitamins. On a day when Hayes was
away, Novitch approved the petition, increasing the acceptable daily
intake level for humans by nearly half, from 34 mg to 50 mg per kilogram
of body weight.
Novitch, now in private industry, said he and Hayes had worked together
on the matter, but declined to say why he was left to sign the approval.
Just weeks later, Hayes resigned under the cloud of an internal Dept. of
Health and Human Services investigation into his acceptance of
gratuities from FDA-regulated companies ≠ including free rides aboard
jets owned by a major NutraSweet user, the General Foods Corp.
Shortly after being named Dean of the New York Medical school, Hayes
also became a consultant to the New York-based public relations firm of
Burson-Marsteller, which represents the NutraSweet Co. and several major
users.
Hayesí former top spokesman, Wayne Pines, who previously had joined the
firm, said he approached Hayes because he thought him "an added value"
to clients.
Hayes, now president of the E.M. Pharmaceutical Co. in Hawthorne, N.Y.,
declined comment for this series of articles. He has in the past denied
any impropriety in his consulting role, which sources said paid him more
than $1000. per day.
Burson-Marsteller vice president, Buck Buchwald stressed that Hayes was
not involved in NutraSweet issues and worked but 10 to 15 days a year.
But a former Burson-Marsteller employee, who requested anonymity, said
Hayes was hired precisely because of his decision on NutraSweet and
other issues affecting company clients.
Sen. Metzenbaum said it was "at the very leastÖunbecoming, at the very
most, it probably was inappropriate" for Hayes to accept the position.
In July 1986, Anthony Brunetti, a FDA consumer product officer who
drafted the 1983 notice approving NutraSweet use in soft drinks, also
took an industry job, joining the soft drink association as a science
advisor. Brunetti said he cleared the move with the FDAís ethics
officer.
"My situation," he said, "is no different than many, many peopleÖthat
go through the revolving door. It can be made to look like there is some
duplicity going on. In terms of my own conscious, I have no problem."
Ron Lorentzen, an FDA toxicologist who was asked by current Bureau of
Foods chief Sanford Miller to perform a separate, internal review of the
agencyís handling of aspartame, described it as a "tortured" story.
But despite the myriad questions and revolving door issues, he asserted
the FDA responded to each issue "in a way, perfectly reasonable." Other
questions have arisen over the company and industryís funding of
researchers who have invariably supported NutraSweetís safety ≠ with the
exception of people with the rare disease phenylketonuria. Independent
studies have often raised health concerns.
Dr. Lewis Stegink, a pediatrics professor at the University of Iowa who
repeatedly has produced studies, that he says, support aspartameís
safety, has received more than $1.3 million dollars in research grants
and gifts, including lab equipment, from the (NutraSweet) company since
the early 1970ís, limited university records show.
Metzenbaum said, "If it is a fact that no questions were raised and
more than a million dollars was spent, you have to wonder whether their
job was done thoroughly as it should be done."
Steginkís longtime research collaborator, Dr. Jack Filer, serves as
executive director of the ILSI (International Life Sciences Institute),
the Washington foundation that funds aspartame research.
Filer said he sees no conflict in his dual roles as ILSIís executive
director and a company researcher, but declined to disclose his ILSI
consulting fees. He said all the Iowa research money has gone to
Stegnik.
Filer also said the company (NutraSweet) paid him and Setgnik "$2,000.
to $3,000." to edit a book, "Aspartame," about research on the
sweetener, and another $1,000. or $1,500. to each of the contributors,
including researchers whose studies helped the company win FDA approval.
The book states that "the extensive research program carried out to
demonstrate aspartame safety may serve as a new standard for the study
of food additives." Filer said he had been "maligned over the years for
taking money from corporations," but that the funding source never has
influenced his findings.
Dr. David Hunninghake of the University of Minnesota was picked to
study aspartameís effect on the liver by former Searle research director
Daniel Azarnoff, once Hunninghakeís mentor at the University of Kansas,
a Hunninghake associate said. He said Searle helped design the study.
Susan Schiffman, named to head a Searle-funded Duke University medical
School study into NutraSweetís link to headaches, is a former General
Foods and Searle consultant. Her research at Duke, where the medical
school has a new Searle Center, has fallen under the office of
university vice president William Anylan, a former Searle director.
Schiffman said Anylan had no role in Searleís promise to cover all costs
of the study, which is expected to cost "hundreds of thousands of
dollars." She said she took no salary for her work.
Another industry-backed researcher has been Ann Reynolds, now
chancellor of California State University at Long Beach. Dr. John Olney
asserted that in a 1971 study, Reynolds confirmed his findings that the
sweetener destroyed nerve cells in infant mice, but Searle did not
notify the FDA until 1975 or 1976, after the FDAís initial review. Dr.
Daniel Azarnoff, Searleís former science director, and other Searle
officials have denied withholding any studies from the government.
Reynolds also co-authored a Searle monkey study that contradicted
earlier aspartame research leading to seizures in monkeys. Dr. Olney
alleged that Reynolds, who did not return phone calls, and several other
company-funded researchers "have a pattern of avoiding" scientific peer
review. Industry spokesmen contend that few studies by scientific
critics of NutraSweet have undergone peer review. But few such clinical
studies have been completed because of a funding shortage.
George Liepa, a nutrition professor at Texas Womanís University said he
was required to discuss his findings with Searle before reporting that
NutraSweet "is safe" for diabetics on hemodialysis. Dr. David Horwitz,
an associate professor of medicine at the University of Illinois, who
studied NutraSweet and diabetics, said the company did not influence the
outcome, But, "The results were favorableÖ. Obviously, that is perhaps
why Searle was eager to fund an additional study of ours."
Dr. Richard Wurtman was an ardent defender of NutraSweetís safety at
public hearings six years ago (1981). Now he is one of the artificial
sweetenerís harshest critics.
"I think the likelihood is very strong that NutraSweet does produce
serious and potentially damaging brain effects in a number of people,"
the nationally known neuroscientist from Massachusetts Institute of
Technology said in a recent series of interviews.
Wurtmanís seemingly enigmatic flip-flop from a position as a G.D.
Searle Co. consultant to a role as a foe urging restrictions on
marketing the firmís best-selling product appears to be much at the
center of the controversy over NutraSweetís safety.
Wurtman says his views simply changed with the evolution of his
scientific studies and his growing skepticism of industries attitude
toward research.
His sometimes stormy relationships with the company and an industry-
funded foundation, the ILSI, provide a glimpse of the maneuverings
surrounding research into a major food additive.
Wurtman, a brash-talking, hard-driving head of a major research
laboratory, said he unilaterally severed his consulting relationship
with Searle in 1985 after he grew concerned about NutraSweetís effects
and the companyís inaction. He said he rejected several approaches by
the firm, (the NutraSweet Co.) since its sale that year to the Monsanto
Corp., to rekindle the consulting arrangement.
Wurtman accuses NutraSweet Co. officials of "misrepresenting" the
nature of company-financed studies into links between the sweetener,
generically known as aspartame, and epileptic seizures, of sidestepping
key safety issues, and of threatening to veto his grant application to
ILSIís aspartame committee.
A spokesman for the NutraSweet Co. described Wurtmanís public attacks
as a "political issue," but declined to elaborate.
Wurtmanís relationship with Searle, The NutraSweet Co., and many of the
companies that sell NutraSweet-flavored products dates to 1978.
Beginning that year, according to public records, ILSI provided more
than $200,000. to finance his research on caffeine, a common beverage
ingredient that was under FDA scrutiny.
Wurtman said he found no ill health effects during his caffeine
research, and his relationship was "excellent" with ILSI ≠ a spinoff of
the National Soft Drink Association.
During the same period in 1978, he said he rejected a Searle offer of
financial support for research on amino acids. Phenylalanine and
aspartic acid, two such amino acids, are the main components of
NutraSweet.
He said Dr. Sanford Miller, chief of FDAís Bureau of Foods, later
sought his testimony before a 1980 Public Board of Inquiry because he
openly stated his belief that neither glutamate nor aspartic acid, a
similar compound to that in NutraSweet, would not cause brain damage.
Wurtman strongly defended aspartame at the hearing.
He said he did not focus on phenylalanine until about 1983, when he
learned the FDA was considering expanding use of the low-calorie
sweetener, approved two years earlier for dry foods, to include
carbonated soft drinks.
From his caffeine research, Wutman said, he was aware of the exploding
soft drink market and concluded "that the use of aspartame was going to
go up considerably."
"I was genuinely concerned that there might be an increase in brain
phenylalanine levels."
Wurtman said that, while phenyalanine is vital to the brain, it can
serve as a barrier to 20 other amino acids that provide protein.
At a meeting in July 1983, Wurtman said he told National Soft Drink
Association officials that "if you put large amounts of aspartame in
soft drinks and people drink as much as I think they will, there are
going to be problems."
Wurtman said that after the industry accepted his idea for combining
NutraSweet with saccharin to cut the danger level, he accepted a Searle
offer to serve as consultant and relations were "all very friendly and
chummy".
Wurtman said he became "convinced that these people really want to know
the extent to which their product may be a real problem".
Shortly after he took the consulting job, he began getting letters from
seizure victims who believed their problems stemmed from NutraSweet.
Wurtman said he when advised Dr. Gerald Gaull, Searle vice president
for nutrition and medical affairs, in the Spring of 1985 that he thought
there was a link, "there was a very rapid souring of their
relationship".
During a visit to his MIT laboratory, Wurtman said, Gaull asked him to
review a proposal for a seizure study by him and his collaborator,
Harvard University neurologist Donald Schomer. He charged that when he
advised Gaull the pair would seek funding from ILSI, Gaull "got very
angry" and said, "We (meaning Searle), are active members of the ILSI
and we will veto your study".
"I was incredulous that he would say it to me, and I was dumbfounded
that he would say it in front of a witness," Wurtman said.
Schomer said he did not recall the comment. Gaull said, "There is no
way that I can veto anything at ILSI," because Searle has only one of 12
votes on the ISLI aspartame committee. He did not deny making the
threat.
Wurtman charged that Gaull later advised ISLI that two company-funded
seizure studies already were under way, and the foundation declined to
approve Wurtmanís grant.
In July of 1985, Wurtman said, he and three other scientists who had
expressed concerns about NutraSweet were among a group invited to
Gaullís home in Northeast Harbor, Maine, for a two-day conference.
"I left there with the conclusion there was no way these people were
going to do an honest job in assessing the possibility that aspartame
contributed to seizures," Wurtman said.
He said he also was skeptical because, as a company consultant, Searle
had asked him to chair its scientific advisory committee, a role in
which the company could use his name to defend the integrity of its own
research. But, he said, Searle refused to let him see protocols and data
from its studies.
"They wanted the name, but not the reality," he said. Frustrated by
these developments, Wurtman said he wrote a letter to Robert Shapiro,
president of Searle and later of the NutraSweet Co.
"Dear Bob," the letter said, "I know youíll agree that my value to
SearleÖ derives in part from my telling the company some things that it
would rather not hearÖand 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 dietsÖ 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."
He said Shapiro never answered the letter.
Wurtman said he resigned his consulting role a short time later and
rejected company efforts in the ensuing months to reinstate the
arrangement.
