Author: Colin Gorenstein

Alzheimer’s drug research continues to look to the future, toward new drugs that might one day treat the ravaging symptoms of the neurodegenerative disease, such as memory loss and even lead to a cure. However, a research team out of the University of Manchester in the UK, led by neuroimmunologist David Brough, has taken their work in the opposite direction, looking at old drugs that are successfully reversing memory loss in a mouse model. Their findings were published in the journal Nature Communications.

When it comes to understanding what causes the dangerous buildup of amyloid plaques and tau tangles in the brain that are prevalent in Alzheimer’s, “evidence is building for inflammation,” neuroimmunologist Jack Rivers-Auty, a co-author on the paper, tells mental_floss. “It’s a bit like when you roll your ankle—you put ice on it to reduce swelling because you’re worried about inflammation causing more damage,” he says. “Inflammation is a very complex process made up of many cell types and proteins… many of which may be causing collateral damage in the brain.”

He and neuroimmunology colleague Mike Daniels conducted experiments on mice after their lab director theorized that common non-steroidal anti-inflammatory drugs (NSAIDs) might inhibit a key inflammatory pathway in the brain that damages brain cells, called the NLRP3 inflammasome complex. “I screened a number of drugs against the inflammasome with cells in a dish,” Daniels tells mental_floss. He was expecting ibuprofen and other more well-known drugs to be the most potent, but in fact, “they had no effect,” he says.

What did work was a less commonly known NSAID called mefanimic acid, which is mainly used for menstrual pain, he says. It worked because it has a different structure. Classic NSAIDs inhibit a protein called cyclooxygenase, whereas mefanimic acid inhibits the inflammasome complex itself.

Next they tested the drugs in a double-blind, placebo-controlled study on mice that were at an age when memory deficits begin to show up, approximately 15 months old. Rivers-Auty says if they were to translate this into a clinical setting with humans, “we would want to aim for people who have just started Alzheimer’s disease. Alzheimer’s [partly causes] the death of neurons, and it’s hard to grow new neurons.”

They used a range of memory tests on the mice to determine whether their memory was in decline before administering mefanimic acid. The most common among them is called the novel object recognition test. This test is useful because mice, like us, are sensitive to unfamiliar objects. Imagine you enter a parking lot looking for your car. In the lot, you find only two objects: your car and an alien’s spaceship. “You would spend more time exploring the spaceship because you hadn’t seen it before,” Rivers-Auty says.

Mice will behave similarly. But what happens if their memory is deficient? To find out, the team gave 10 mice a placebo, while the other 10 were treated with mefanimic acid via a subcutaneous pump for 28 days. The study found that “the mouse with good memory explores the new object, and the mouse with poor memory explores them both,” Rivers-Auty explains. 

At the end of the study, the mice that had been given the mefanimic acid “did not have memory deficits,” he says. The drug had restored memory function to the mice with failing memory.

The results were so surprising to them, Rivers-Auty says, “We were literally hooting and hollering. We couldn’t believe how well it worked. It’s very unusual for groups to reverse memory deficits.”

The team is hopeful that this discovery could bypass as much as 15 years of the usual process to develop a new drug because mefanimic acid is already in use by humans and has been deemed safe. “We can skip the extensive animal testing and the first stage of human trials,” says Rivers-Auty. “This saves a huge amount of time and money.”

However enthusiastic he and his colleagues are about their results, Rivers-Auty is skeptical that the team will find commercial funding sources for the next stage of trials in humans because “pharmaceutical companies who usually fund these studies have no interest in funding a study they can’t make money off,” he says. Instead, this team relies on charities such as the Alzheimer’s Society and Alzheimer’s Research UK, which funded their work.

If you visited an older, well-established McDonald’s franchise during the latter part of the 1990s—specifically one of the corporation’s two-story restaurants boasting a “McDonald’s PlayLand”—you may have noticed some odd shapes and unfamiliar characters featured on the playground’s equipment. This was long before ball pits: The cornerstone of many a PlayLand (today referred to as a “PlayPlace”) was a huge blue-painted tower, topped by a pod that approximated a Big Mac sandwich with painted eyes and a hat that functioned as a climb-in jail, and an assortment of individual carousel horses sporting the head of a hamburger, a Filet-O-Fish sandwich, or other colorful craniums reminiscent of shaggy pom-poms with large, soulful eyes.

These outdated PlayLands featured aspects (or integrated whole character pieces) of characters from “McDonaldland”: A mass-market television campaign, launched in 1971, that established a fictional universe which was inhabited by Ronald McDonald and his comrades. Although advertising then was chock-full of colorful characters like Ronald McDonald—this was, after all, around the time that Fred Flintstone and Barney Rubble began hawking Pebbles, and the Kool-Aid man started busting through walls—concocting an entire fictional world for the purpose of selling a product was a different story. This ingeniously effective format targeted kids at a very early age, introducing them to various McDonald’s menu items with the assistance of friendly mascots beyond Ronald McDonald—a character that, according to McDonald’s, “is second only to Santa Claus in terms of [brand] recognition … 96% of all schoolchildren in the United States of America recognize Ronald.”

COOKING UP MCDONALDLAND

In 1970-71, at the behest of the McDonald’s Corporation, the advertising agency Needham, Harper & Steers created a fantastic imaginary world they dubbed McDonaldland, and a cast of characters to populate it: Officer Big Mac, Grimace (a revision of a character who was once a four-armed villain), the Hamburglar, Mayor McCheese, the [Mad] Professor, Captain Crook and, of course, Ronald McDonald. The agency generated these characters and their world out of essentially nothing, using the McDonaldland Brand Specification Manual.

THE TOYS

It’s probably no surprise that a line of toys would follow McDonald’s uber-successful ad campaign. In 1976, Remco (then a subsidiary of Azrak-Hamway International) produced a line of 6-inch-tall action figures to celebrate the iconic McDonaldland characters.

Remco was infamous for cobbling together inferior action figures in record time, but the McDonaldland action figures stood out against the company’s simple fare. The fully poseable dolls had multi-piece cloth outfits with stenciled and dyed fabric details, hard and soft plastic outfit accoutrements, and, with the exception of Grimace and Ronald, an interesting character-specific accessory. (Officer Big Mac had a badge, for example, while Mayor McCheese came with glasses and a sash.) Each toy also included a small protruding lever on its back that, when manipulated, would cause the character’s head to bob up-and-down or side-to-side (for all except Grimace). The high-quality pieces were Remco’s crowning achievement during the 1970s.

Ronald McDonald
McDonald’s primary mascot, a proud inhabitant of the fantasy world of McDonaldland, Ronald was first created and portrayed by television personality Willard Scott in 1963. Scott (a local radio host who also played Bozo the Clown on WRC-TV in Washington D.C. from 1959 to 1962) performed while using the name “Ronald McDonald, the Hamburger-Happy Clown” in three television commercials.

Ronald’s Remco action figure had high-quality rooted red hair and a body with red limbs, painted red hands, non-removable oversized shoes and molded socks. He wore a yellow clown jumpsuit with red-and-white-striped sleeves and non-removable dickey that had three functional vinyl pockets, and the jumpsuit could be snapped on or removed.

Officer Big Mac
With a double-decker head based on what would one day become the most iconic fast food sandwich in history—the McDonaldland advertising campaign was established in 1971, a mere three years after the Big Mac sandwich was introduced nationally—Remco’s Officer Big Mac was dressed to resemble a member of the Keystone Cops and replicated the silent film stars’ incompetence. As McDonaldland’s Chief of Police, Officer Big Mac’s appointed task was to prevent Captain Crook and the Hamburglar from stealing Filet-O-Fish and hamburger sandwiches, respectively.

The head of the Remco action figure was rendered in a soft plastic similar to that of a squeaky toy, and came with a silver whistle; plastic belt with the “M” logo; blue overcoat with decorative silver buttons and a hemmed collar; blue pants with elastic waistband and cuffs; and a silver fabric “star” label. Although the costume was removable, the character’s shoes were not, so anyone undressing the figure would have to take care—the delicate fabric tended to snag and pull.

Captain Crook (a.k.a. The Captain)
Based on the designs of Disney’s Captain Hook from Peter Pan (1953), Captain Crook was one of the two major adversaries of McDonaldland (along with the Hamburglar), who—as a seafaring villain—was obsessed with stealing Filet-O-Fish sandwiches. Eventually, his surname was dropped, his personality mellowed, and the character became known simply as “The Captain”—like the Hamburglar, his sinister countenance was modified to make his appearance seem more kid-friendly. As was the case with many of these characters, Captain Crook was eliminated from advertisements during the 1980s when the concept of McDonaldland was streamlined.

His Remco action figure came with a soft plastic orange sword (removable); a removable bircorne pirate’s hat with golden trim and a golden C (for Captain); a coat with lace cuffs, a lace ascot, hard plastic brown epaulets, and a two-piece removable dickey; and removable breeches with cuffs and an elastic waistband. The figure has one non-removable gold earring in its right ear.

Grimace
Originally sporting four arms and designed to be an adversary of Ronald McDonald, Grimace’s initial manifestation was quite different from the sweet, child-friendly dullard we grew to love in the ‘70s and ‘80s. Renowned for beginning each sentence with the word “duh,” both versions of Grimace are quite fond of McDonald’s Triple Thick Milkshakes. The latter, friendlier form of Grimace was retained by McDonald’s even after the corporation shut down their McDonaldland advertising campaign. He stuck around for decades, until approximately 2003.

Remco’s Grimace action figure wasn’t constructed of solid plastic like the other dolls. Instead, the doll had a furred purple felt outer body, with innards similar to the polystyrene material found inside of a bean bag. Calling Remco’s Grimace an “action figure” is a bit of a stretch, since the toy had very limited poseability: His arms and hands were flaps of furred purple felt, while his hard-plastic purple feet allowed him to stand. Even his expression—rendered by hard plastic eyebrows, eyes, and a mouth—was immobile.

Hamburglar
Initially called “The Lone Jogger,” the Hamburgular’s personality traits and design changed quite a bit over the course of the three decades during which he existed (like Grimace, he was retired in 2003). Originally, this character was a truly frightening scoundrel with stringy grey hair and a menacing black mask and cape; McDonald’s decided to soften the character’s disposition in order to make his personality more palatable for children. Throughout the years, however, the essence of McDonaldland’s preeminent villain remained the same: a compulsive criminal obsessed with burgling hamburgers. 

With his mischievous grin, pair of prominent, rat-like central incisors, short stature, pointed nose, and peculiar clothing, the Hamburglar action figure’s early design sold quite well for Remco. The figure wore a removable striped convict outfit, polka-dotted plastic tie, and soft plastic hat brim (the top of his hat was molded atop his head, and the thin, round, plastic brim slid around it). In the early 1970s, the Hamburglar’s characteristic speech patterns were absolutely unintelligible to anyone but Captain Crook, who was kind enough to translate for the inhabitants of McDonaldland. Eventually, the Hamburglar would issue forth an occasional exclamation of “Robble, robble!”

The Professor
Originally known as the “Mad” Professor, in early appearances the character rarely spoke and functioned as a second-tier, background personality. Later in the McDonaldland campaign (around 1973 to 1975), the bearded and bespectacled Professor appeared more often and spoke in a high-pitched, excitable, academic manner about his latest zany invention—usually a device created to preserve the well-being of the good citizens of McDonaldland.

In the 1970s, the character appeared as a prototypical absent-minded scientist (note the two pairs of glasses molded onto the action figure’s head; one pair he wears, while the other is balanced on his forehead). He sported long, thinning gray hair with a full gray beard, and wore a long white lab coat featuring pockets bursting with tools and implements. The lab coat has two front pockets that could indeed hold items, but instead (to save money on tooling and plastic) the toy company decided to create thin fabric stickers with two-dimensional images of tools, which were factory-applied to draw attention to these bulging pockets. The action figure came with a silver wrench and a removable, two-piece red scarf.

In the 1980s, the Professor’s physical appearance was entirely reconfigured into a much sweeter, more kid-friendly scientist. Slightly balding with short white hair, a Franz Joseph-style beard, and black glasses worn over a pair of excited bright eyes, the newer Professor was largely unrecognizable from his previously established version of the 1970s.

Mayor McCheese
The iconic Mayor McCheese, who had a cheeseburger as a head, functioned as the unequivocally incompetent head of McDonaldland’s government. Regardless of which actor provided his voice in the McDonaldland commercials, the superbly quirky delivery for Mayor McCheese was directly based upon the late comedian Ed Wynn, who provided the voice for the Mad Hatter in Disney’s Alice in Wonderland.

The Remco Mayor McCheese doll comes complete with a bevy of impressive accessories, including removable yellow pince nez glasses; a removable purple sash emblazoned with the letter M; a fuschia tuxedo jacket with soft white plastic lapels; a removable soft white plastic flower with faux pearl; and a pinstripe sleeveless tuxedo jumpsuit with attached yellow vest.

THE PLAYSET

To complement these seven figures, Remco also made a superbly detailed McDonaldland playset, which even came with its own stationery (above). “Welcome to the fun and excitement of McDonaldland,” the back of the box read. “There’s so much to do”:

“The gathering place for Ronald McDonald and all the McDonaldland characters. Take a ride on the colorful wind up train featuring a Locomotive, Passenger Car and a Hamburglar Paddy Wagon, also seven pieces of track and a Stop-N-Go Signal Switch. Play with the swing on the enchanting Apple Pie Tree. Cross the Filet-O-Fish Lake via the Golden Arches Bridge. Put Ronald on stilts for real clown fun. Serve a tray with McDonald’s hamburger and drink at the famous McDonald’s Family Restaurant. All this on a 28 ½” x 30” Playland surface enhanced by an 11” colorful backdrop. Words for the ‘McFavorite Clown Song’ are printed on the play surface. Special McDonald’s Letterland Stationery included for personal messages. All plastic parts molded of strong, safe, non-toxic materials. Surely THE fun place to be.”

Today, it’s nearly impossible to find this playset unbroken, intact, and complete with all of its many delicate pieces and parts that were prominently featured in McDonald’s advertising campaign.

Compare Remco’s playset to the corporate image of the real-world fantasyland as built by Needham, Harper & Steers and taken from the McDonaldland Specification Manual. Remco’s set is astonishingly well-rendered.

THE LAWSUITS

It didn’t take long for McDonaldland to come under attack. Mayor McCheese possessed a number of similarities to another personality created by producers Sid and Marty Krofft: H.R. Pufnstuf, who featured prominently on Saturday morning lineups from 1969 to 1973. Both McCheese and Pufnstuf were rendered as live-action, life-sized puppets with ridiculously large heads, and both had mayoral sashes as heads of their respective governments. (And while McCheese had an M or “mayor” written on his sash, Pufnstuf had a medal which hung down from the cummerbund and said “mayor.”)

The similarities didn’t end with the characters. Just as Mayor McCheese lived in McDonaldland, H.R. Pufnstuf inhabited his own imaginary realm, Living Island. Both fantasylands were comprised of similarly-rendered “magical” creatures, buildings, and backgrounds—which made sense, since Sid and Marty Krofft had been consulted by Needham, Harper & Steers before they landed the McDonald’s account. According to the Krofft’s lawsuit,

“In early 1970, Marty Krofft … was contacted by an executive from Needham, Harper & Steers, Inc., an advertising agency. He was told that Needham was attempting to get the advertising account of McDonald’s hamburger restaurant chain and wanted to base a proposed campaign to McDonald’s on the H. R. Pufnstuf characters. The executive wanted to know whether the Kroffts would be interested in working with Needham on a project of this type.

So in 1971, the Kroffts, believing that McDonald’s characters were based directly upon their own life-sized puppets, engaged in a series of legal battles with the McDonald’s corporation. In the midst of the conflict—a full five years after the Kroffts began pursuing litigation—Remco was asked to produce the fully-licensed toys for McDonald’s in 1976.

After a six-year battle, the courts ruled in the Kroffts’ favor. In Sid & Marty Krofft Television Productions Inc. v. McDonald’s Corp., the plaintiffs proved copyright infringement, showing: a) their ownership of [the] copyrighted work, b) the circumstantial evidence of access to work, and c) that there was a substantial similarity in both idea and expression. “We do not believe that the ordinary reasonable person, let alone a child, viewing these works will even notice that Pufnstuf is wearing a cummerbund while Mayor McCheese is wearing a diplomat’s sash,” the appeals court stated. Predicting the defendant’s appeal based upon the “Look and Feel” defense, the court concluded that McDonald’s had unjustly utilized the “total concept and feel” of the Krofts’ H.R. Pufnstuf program. McDonald’s was required to cease production of (many of) the characters and stop airing television commercials featuring the denizens of McDonaldland. They were also ordered to pay the Kroffts more than $1 million: $6000 for each commercial, $5000 for each promotional item, and $500 for other infringing acts.

Although some of these characters have been gone for nearly 40 years, the action figures survive as collectibles, making regular appearances on eBay. But what happened to the characters? A few years ago, I posed this question to McDonald’s then-Media Center Contact/Corporate Communications and Social Responsibility Team leader, Julie Pottebaum. Here—verbatim—was her reply: “Mayor McCheese and his friends are indeed alive and well, enjoying life in McDonaldland. Ronald McDonald has taken over the mayor’s responsibilities since being appointed Chief Happiness Officer. Ronald McDonald remains front and center, and he reminds us of the kid that lives in all of us.”

All photos courtesy of Mark Bellomo