How Aspartame Became Legal – The Timeline

In 1985 Monsanto purchased G.D. Searle, the chemical company that held the patent to aspartame, the active ingredient in NutraSweet. Monsanto was apparently untroubled by aspartame’s clouded past, including a 1980 FDA Board of Inquiry, comprised of three independent scientists, which confirmed that it “might induce brain tumors.”

The FDA had actually banned aspartame based on this finding, only to have Searle Chairman Donald Rumsfeld (currently the Secretary of Defense) vow to “call in his markers,” to get it approved.

On January 21, 1981, the day after Ronald Reagan’s inauguration, Searle re-applied to the FDA for approval to use aspartame in food sweetener, and Reagan’s new FDA commissioner, Arthur Hayes Hull, Jr., appointed a 5-person Scientific Commission to review the board of inquiry’s decision.

It soon became clear that the panel would uphold the ban by a 3-2 decision, but Hull then installed a sixth member on the commission, and the vote became deadlocked. He then personally broke the tie in aspartame’s favor. Hull later left the FDA under allegations of impropriety, served briefly as Provost at New York Medical College, and then took a position with Burston-Marsteller, the chief public relations firm for both Monsanto and GD Searle. Since that time he has never spoken publicly about aspartame.

The Aspartame/NutraSweet Timeline

http://www.swankin-turner.com/aspartame.html
http://www.swankin-turner.com/hist.html

Aspartame/NutraSweet: The History of the Aspartame Controversy

By James Turner, ESQ. Director of the National Institute of Science, Law, and Public Policy (NISLAPP)

National Institute of Science, Law, and Public Policy 1400 16th Street, NW, Suite 330, Washington, DC 20036 (202) 462-8800 Fax: (202) 265-6564 nislapp@swankin-turner.com

Timeline

December 1965– While working on an ulcer drug, James Schlatter, a chemist at G.D. Searle, accidentally discovers aspartame, a substance that is 180 times sweeter than sugar yet has no calories.

Spring 1967– Searle begins the safety tests on aspartame that are necessary for applying for FDA approval of food additives.

Fall 1967– Dr. Harold Waisman, a biochemist at the University of Wisconsin, conducts aspartame safety tests on infant monkeys on behalf of the Searle Company. Of the seven monkeys that were being fed aspartame mixed with milk, one dies and five others have grand mal seizures.

November 1970– Cyclamate, the reigning low-calorie artificial sweetener — is pulled off the market after some scientists associate it with cancer. Questions are also raised about safety of saccharin, the only other artificial sweetener on the market, leaving the field wide open for aspartame.

December 18, 1970– Searle Company executives lay out a “Food and Drug Sweetener Strategy’ that they feel will put the FDA into a positive frame of mind about aspartame. An internal policy memo describes psychological tactics the company should use to bring the FDA into a subconscious spirit of participation” with them on aspartame and get FDA regulators into the “habit of saying, “Yes”.”

Spring 1971– Neuroscientist Dr. John Olney (whose pioneering work with monosodium glutamate was responsible for having it removed from baby foods) informs Searle that his studies show that aspartic acid (one of the ingredients of aspartame) caused holes in the brains of infant mice. One of Searle’s own researchers confirmed Dr. Olney’s findings in a similar study.

February 1973– After spending tens of millions of dollars conducting safety tests, the G.D. Searle Company applies for FDA approval and submits over 100 studies they claim support aspartame’s safety.

March 5, 1973– One of the first FDA scientists to review the aspartame safety data states that “the information provided (by Searle) is inadequate to permit an evaluation of the potential toxicity of aspartame”. She says in her report that in order to be certain that aspartame is safe, further clinical tests are needed.

May 1974– Attorney, Jim Turner (consumer advocate who was instrumental in getting cyclamate taken off the market) meets with Searle representatives to discuss Dr. Olney’s 1971 study which showed that aspartic acid caused holes in the brains of infant mice.

July 26, 1974– The FDA grants aspartame its first approval for restricted use in dry foods.

August 1974– Jim Turner and Dr. John Olney file the first objections against aspartame’s approval.

March 24, 1976– Turner and Olney’s petition triggers an FDA investigation of the laboratory practices of aspartame’s manufacturer, G.D. Searle. The investigation finds Searle’s testing procedures shoddy, full of inaccuracies and “manipulated” test data. The investigators report they “had never seen anything as bad as Searle’s testing.”

January 10, 1977– The FDA formally requests the U.S. Attorney’s office to begin grand jury proceedings to investigate whether indictments should be filed against Searle for knowingly misrepresenting findings and “concealing material facts and making false statements” in aspartame safety tests. This is the first time in the FDA’s history that they request a criminal investigation of a manufacturer.

January 26, 1977– While the grand jury probe is underway, Sidley & Austin, the law firm representing Searle, begins job negotiations with the U.S. Attorney in charge of the investigation, Samuel Skinner.

March 8, 1977– G. D. Searle hires prominent Washington insider Donald Rumsfeld as the new CEO to try to turn the beleaguered company around. A former Member of Congress and Secretary of Defense in the Ford Administration, Rumsfeld brings in several of his Washington cronies as top management.

July 1, 1977– Samuel Skinner leaves the U.S. Attorney’s office and takes a job with Searle’s law firm. (see Jan. 26th)

August 1, 1977– The Bressler Report, compiled by FDA investigators and headed by Jerome Bressler, is released. The report finds that 98 of the 196 animals died during one of Searle’s studies and weren’t autopsied until later dates, in some cases over one year after death. Many other errors and inconsistencies are noted. For example, a rat was reported alive, then dead, then alive, then dead again; a mass, a uterine polyp, and ovarian neoplasms were found in animals but not reported or diagnosed in Searle’s reports.

December 8, 1977– U.S. Attorney Skinner’s withdrawal and resignation stalls the Searle grand jury investigation for so long that the statue of limitations on the aspartame charges runs out. The grand jury investigation is dropped.

June 1, 1979– The FDA established a Public Board of Inquiry (PBOI) to rule on safety issues surrounding NutraSweet.

September 30, 1980– The Public Board of Inquiry concludes NutraSweet should not be approved pending further investigations of brain tumors in animals. The board states it “has not been presented with proof of reasonable certainty that aspartame is safe for use as a food additive.”

January 1981– Donald Rumsfeld, CEO of Searle, states in a sales meeting that he is going to make a big push to get aspartame approved within the year. Rumsfeld says he will use his political pull in Washington, rather than scientific means, to make sure it gets approved.

January 21, 1981– Ronald Reagan is sworn in as President of the United States. Reagan’s transition team, which includes Donald Rumsfeld, CEO of G. D. Searle, hand picks Dr. Arthur Hull Hayes Jr. to be the new FDA Commissioner.

March, 1981– An FDA commissioner’s panel is established to review issues raised by the Public Board of Inquiry.

May 19, 1981– Three of six in-house FDA scientists who were responsible for reviewing the brain tumor issues, Dr. Robert Condon, Dr. Satya Dubey, and Dr. Douglas Park, advise against approval of NutraSweet, stating on the record that the Searle tests are unreliable and not adequate to determine the safety of aspartame.

July 15, 1981– In one of his first official acts, Dr. Arthur Hayes Jr., the new FDA commissioner, overrules the Public Board of Inquiry, ignores the recommendations of his own internal FDA team and approves NutraSweet for dry products. Hayes says that aspartame has been shown to be safe for its’ proposed uses and says few compounds have withstood such detailed testing and repeated close scrutiny.

October 15, 1982– The FDA announces that Searle has filed a petition that aspartame be approved as a sweetener in carbonated beverages and other liquids.

July 1, 1983– The National Soft Drink Association (NSDA) urges the FDA to delay approval of aspartame for carbonated beverages pending further testing because aspartame is very unstable in liquid form. When liquid aspartame is stored in temperatures above 85 degrees Fahrenheit, it breaks down into DKP and formaldehyde, both of which are known toxins.

July 8, 1983– The National Soft Drink Association drafts an objection to the final ruling which permits the use of aspartame in carbonated beverages and syrup bases and requests a hearing on the objections. The association says that Searle has not provided responsible certainty that aspartame and its’ degradation products are safe for use in soft drinks.

August 8, 1983– Consumer Attorney, Jim Turner of the Community Nutrition Institute and Dr. Woodrow Monte, Arizona State University’s Director of Food Science and Nutritional Laboratories, file suit with the FDA objecting to aspartame approval based on unresolved safety issues.

September, 1983– FDA Commissioner Hayes resigns under a cloud of controversy about his taking unauthorized rides aboard a General Foods jet. (General foods is a major customer of NutraSweet) Burson-Marsteller, Searle’s public relation firm (which also represented several of NutraSweet’s major users), immediately hires Hayes as senior scientific consultant.

Fall 1983– The first carbonated beverages containing aspartame are sold for public consumption.

November 1984– Center for Disease Control (CDC) “Evaluation of consumer complaints related to aspartame use.” (summary by B. Mullarkey)

November 3, 1987– U.S. hearing, “NutraSweet: Health and Safety Concerns,” Committee on Labor and Human Resources, Senator Howard Metzenbaum, chairman.

********************

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in aspartame toxicity research 7.31.2 rmforall

http://www.dorway.com/upipart1.txt
UPI reporter Gregory Gordon: 96K 3-part expose Oct 1987

“Survey of aspartame studies: correlation of outcome and funding sources,” 1998, unpublished: http://www.dorway.com/peerrev.html Walton found 166 separate published studies in the peer reviewed medical literature, which had relevance for questions of human safety. The 74 studies funded by industry all (100%) attested to aspartame’s safety, whereas of the 92 non-industry funded studies, 84 (91%) identified a problem. Six of the seven non-industry funded studies that were favorable to aspartame safety were from the FDA, which has a public record that shows a strong pro-industry bias. Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio Universities, College of Medicine, Dept. of Psychiatry, Youngstown, OH 44501, Chairman, The Center for Behavioral Medicine, Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown, OH 44501 330-740-3621 rwalton193@aol.com http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

From Norfolk Genetic Information Network
(Taken from Welcome to the Spin Machine by Michael Manville http://www.freezerbox.com/archive/2001/04/biotech/
http://www.freezerbox.com/

Marijuana Could Prevent Alzheimer’s, New Study

Posted by timothy on Tuesday January 27, @09:36AM

from the that’s-just-like-your-opinion-man dept.
Chickan writes “‘A puff a day might keep Alzheimer’s away, according to marijuana research by professor Gary Wenk and associate professor Yannic Marchalant of the Ohio State Department of Psychology. Wenk’s studies show that a low dosage in the morning of a certain cannabinoid, a component in marijuana, reversed memory loss in older rats’ brains. In his study, an experimental group of old rats received a dosage, and a control group of rats did not. The old rats that received the drugs performed better on memory tests, and the drug slowed and prevented brain cell death.’ My fine university’s dollars at work!” Maybe it works even better in combination with brain-preserving sips of coffee.

Marijuana’s Memory Paradox

Are pot smokers less likely to get Alzheimer’s? A compound similar to the active ingredient in cannabis shows promise as a potential memory protector.

Marijuana isn’t known for being a friend to memory; its short-term effects notoriously impair recall. And although the data is conflicting, some studies link cannabis with memory deficits in those who use excessive doses for long periods of time

But new research suggests that one of the active ingredients in marijuana—THC—and similar compounds could possibly prevent or even reverse one of the most devastating memory disorders of all: Alzheimer’s disease.

In a paper published in the December 2008 issue of the journal Neurobiology of Aging, researchers found that a compound that affects the same brain receptors as THC reduced brain inflammation and improved memory in older rats. (The rodents were the human equivalent of age 65 to 70.) Although there’s debate over the role played by inflammation in Alzheimer’s, many researchers believe it’s an important part of the process that causes dementia.

“We were shocked and surprised that it worked,” says Gary Wenk, Ph.D., one of the study’s authors and a professor of psychology and neuroscience at Ohio State University.

Wenk and his colleagues traced the anti-inflammatory effect of the compound (which has the awkward name “WIN-55,212-2”) to its activation of cannabinoid receptors on brain cells—the same receptors activated by THC.

Other anti-inflammatory compounds studied in rats and humans like NSAID drugs (ibuprofen, etc.) showed effects on young brains, but unlike WIN-55,212-2 did not improve aged brains.

Wenk has also found in these older rats that the  WIN-55,212-2 compound promotes the growth of new brain cells—a process that declines and may even stop in older animals. “The most amazing thing we saw was that it re-initiates neurogenesis—usually, the only drugs that do that are the SSRI antidepressants [selective serotonin re-uptake inhibitors, the class of drugs that includes Prozac].”

Timing is everything

How could a drug that clearly impairs memory while people are under its influence function to protect users’ recall in the long term? Wenk theorizes that this could be due to differences in the way young and old brains learn.

Research shows that the neurotransmitter glutamate is involved in storing memory in a process that involves growing both new cells and connections between them, and destroying old ones. Some current Alzheimer’s drugs like memantine affect glutamate—as does THC.

Early in life, this process is in balance, and so interfering with either the growth or the “pruning back” of brain cells and connections—as might occur from using marijuana—might impair memory. But, says Wenk, “The same systems involved in pruning neurons at the beginning of life could be killing them at the end.” Therefore, interfering with the pruning process later in life might actually help, rather than harm.

No need for a high

Rest assured, Wenk and his colleagues aren’t advocating a stoner lifestyle.

Because WIN-55,212-2, like THC, produces a high, the researchers looked for the lowest effective dose. They estimate that that dose is the equivalent to just one toke of marijuana. “A puff is enough,” Wenk says.

Though that dose wouldn’t get someone high, it could, admittedly, have some psychoactive effect. But this wouldn’t necessarily rule out medical use. The drug could be taken before bedtime, for example. And with long-term use, tolerance to these psychoactive effects can develop, so impairment might be minimal with a steady dose anyway.

Cannabis research is controversial

To find out if THC has a protective effect on humans, scientists could study marijuana smokers as they age. If the theory holds, such users might be expected to develop Alzheimer’s disease at lower rates than non-users—although the timing and extent of use would almost certainly also matter.

Given the controversy that would likely arise if a protective effect were to be discovered, however, no one has funded the epidemiological studies that would be needed to show this.

It’s even hard to get experimental research published, according to Kim Janda, Professor of Chemistry at the Scripps Research Institute in California. In 2006, he published a paper demonstrating that THC interfered with another process implicated in the pathology of Alzheimer’s disease: the formation of amyloid-beta plaques and fibrils.

Janda’s THC research was rejected by several big-name journals and eventually published in the journal Molecular Pharmacology; it’s now one of his most frequently cited articles by fellow scientists. Unfortunately, the article was also denounced in the press by the likes of Rush Limbaugh as an example of politicized science by hidden supporters of legalization—despite the fact that Janda also works on anti-cocaine addiction vaccines.

Although Janda would like to investigate further, he currently does not have grants to enable him to do so.

Why further marijuana studies should be funded

Bill Thies, Ph.D., chief medical and scientific Officer of the Alzheimer’s Association, says of Wenk’s research, “The authors of the paper make the case that one way to modulate the inflammatory reaction is to activate cannabinoid receptors. I think that’s perfectly reasonable basic science.”

Thies notes, however, that it’s a long way from basic science to a usable drug, and pleads for a rational discussion. “The issue of marijuana is highly emotional and political and the minute it’s put in context of legalizing marijuana, the discussion loses all sensible aspects.”

Don Abrams, M.D., chief of hematology/oncology at San Francisco General Hospital, has studied medical marijuana use in people with HIV for more than a decade. He says, “I think the safety profile of marijuana compares very favorably to many other prescribed drugs,” noting that there have not been any reported overdoses, and that most research does not support a link between smoking the drug and lung cancer (which may be because marijuana users  tend to not smoke nearly as much as cigarette smokers).

“Cannabis is anti-inflammatory and it is also an antioxidant, and those are two things that we seek in treating neurodegenerative disorders,” he says, “It’s there, it’s in nature, if the research does find that it has these benefits, why not take advantage of it?”

With five million Americans currently living with Alzheimer’s and no highly effective treatment or prevention method known, any promising lead—even one as politically fraught as marijuana and related synthetics—could be worth following.

Recent Research on Medical Marijuana

Emerging Clinical Applications For Cannabis & Cannabinoids
A Review of the Recent Scientific Literature, 2000 — 2008

Despite continued political debates regarding the legality of medicinal marijuana, clinical investigations of the therapeutic use of cannabinoids are now more prevalent than at any time in history. A search of the National Library of Medicine’s PubMed website quantifies this fact. A keyword search using the terms “cannabinoids, 1996” reveals just 258 scientific journal articles published on the subject for that year. Perform this same search for the year 2007, and one will find over 3,400 published scientific studies.

While much of the renewed interest in cannabinoid therapeutics is a result of the discovery of the endocannabinoid regulatory system, some of this increased attention is also due to the growing body of testimonials from medicinal cannabis patients and their physicians. Nevertheless, despite this influx of anecdotal reports, much of the modern investigation of medicinal cannabis remains limited to preclinical (animal) studies of individual cannabinoids (e.g. THC or cannabidiol) and/or synthetic cannabinoid agonists (e.g., dronabinol or WIN 55,212-2) rather than clinical trial investigations involving whole plant material. Predictably, because of the US government’s strong public policy stance against any use of cannabis, the bulk of this modern cannabinoid research is taking place outside the United States.

As clinical research into the therapeutic value of cannabinoids has proliferated exponentially, so too has investigators’ understanding of cannabis’ remarkable capability to combat disease. Whereas researchers in the 1970s, 80s, and 90s primarily assessed cannabis’ ability to temporarily alleviate various disease symptoms — such as the nausea associated with cancer chemotherapy — scientists today are exploring the potential role of cannabinoids to alter disease progression. Of particular interest, scientists are investigating cannabinoids’ capacity to moderate autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease, as well as their role in the treatment of neurological disorders such as Alzheimer’s disease and amyotrophic lateral sclerosis (a.k.a. Lou Gehrig’s disease.)

Investigators are also studying the anti-cancer activities of cannabis, as a growing body of preclinical and clinical data concludes that cannabinoids can reduce the spread of specific cancer cells via apoptosis (programmed cell death) and by the inhibition of angiogenesis (the formation of new blood vessels). Arguably, these latter trends represent far broader and more significant applications for cannabinoid therapeutics than researchers could have imagined some thirty or even twenty years ago.

HOW TO USE THIS REPORT

As states continue to approve legislation enabling the physician-supervised use of medicinal marijuana, more patients with varying disease types are exploring the use of therapeutic cannabis. Many of these patients and their physicians are now discussing this issue for the first time, and are seeking guidance on whether the therapeutic use of cannabis may or may not be appropriate. This report seeks to provide this guidance by summarizing the most recently published scientific research (2000-2008) on the therapeutic use of cannabis and cannabinoids for 17 separate clinical indications:

* Alzheimer’s disease
* Amyotrophic lateral sclerosis
* Diabetes mellitus
* Dystonia
* Fibromyalgia
* Gastrointestinal disorders
* Gliomas
* Hepatitis C
* Human Immunodeficiency Virus
* Hypertension
* Incontinence
* Multiple sclerosis
* Osteoporosis
* Pruritis
* Rheumatoid arthritis
* Sleep apnea
* Tourette’s syndrome

In some of these cases, modern science is now affirming longtime anecdotal reports of medicinal cannabis users (e.g., the use of cannabis to alleviate GI disorders). In other cases, this research is highlighting entirely new potential clinical utilities for cannabinoids (e.g., the use of cannabinoids to modify the progression of diabetes.)

The diseases profiled in this report were chosen because patients frequently inquire about the therapeutic use of cannabis to treat these disorders. In addition, many of the indications included in this report may be moderated by cannabis therapy. In several cases, preclinical data indicates that cannabinoids may halt the progression of these diseases in a more efficacious manner than available pharmaceuticals. In virtually all cases, this report is the most thorough and comprehensive review of the recent scientific literature regarding the therapeutic use of cannabis and cannabinoids.

For patients and their physicians, let this report serve as a primer for those who are considering using or recommending medicinal cannabis. For others, let this report serve as an introduction to the broad range of emerging clinical applications for cannabis and its various compounds.

Paul Armentano
Deputy Director
NORML | NORML Foundation
Washington, DC
January 24, 2008

* The author would like to acknowledge Drs. Dale Gieringer, Gregory Carter, Steven Karch, and Mitch Earleywine, as well as NORML interns John Lucy, Christopher Rasmussen, and Rita Bowles, for providing research assistance for this report. The NORML Foundation would also like to acknowledge Dale Gieringer, Paul Kuhn, and Richard Wolfe for their financial contributions toward the publication of this report.

** Important and timely publications such as this are only made possible when concerned citizens become involved with NORML. For more information on joining NORML or making a donation, please visit: http://www.norml.org/join. Tax deductible donations in support of NORML’s public education campaigns should be made payable to the NORML Foundation.