Headaches and revelry go together like Scotch and soda, some say, which is why one of the first decisions many people must make, as they wake up on New Year`s Day, is which painkiller to choose. The news, according to two clear-headed writers, is that it doesn`t much matter.
For sufferers, it is probably best to get to the point of this story immediately. Here it is: For headaches, there is no effective difference among commonly available pain relievers. Your instructions, therefore, are to take two aspirin, or Tylenol, or Advil, or other analogous product. Calm down. Read the rest of this story. You`ll feel better
The strange thing, as Charles C. Mann and Mark L. Plummer report in ”The Aspirin Wars: Money, Medicine, and 100 Years of Rampant Competition” (Knopf, $25), is that no one fully understands acetylsalicylic acid, commonly known as aspirin. It works. So do 40 other compounds in the category known as non-steroidal anti-inflammatory drugs. Scientists are still figuring out how.
But it`s big business. As Mann and Plummer note, aspirin is the single most popular drug in the world. In the U.S., 30 billion tablets are consumed each year. Worldwide figures are less certain, but they could reach 100 million pounds annually, a magic mountain of white pills, worth perhaps $25 billion, taken to relieve headaches, reduce fevers, soothe rheumatic pains and perhaps address ailments such as heart attacks and colon cancer.
And along the way, it has produced some advertising legends. Alka-Seltzer, an effervescent, analgesic, alkalizing tablet, based on a home remedy of aspirin, bicarbonate of soda and lemon juice, celebrated its 60th birthday in 1991. Not coincidental to its continued good health, Alka-Seltzer also launched two of the most-watched ads in the history of American TV:
”Plop, plop, fizz, fizz,” and, ”I can`t believe I ate the whole thing.”
Advertising, in fact, is one important way the producers of aspirin and aspirin-based products can differentiate themselves from one another.
”If you`re an average person with an average headache, a dose of any over-the-counter analgesic, which means painkiller, will cure at the same rate,” noted Mann by phone from his country place in the Massachusetts Berkshires. ”It`s like hitting a nail with a hammer. Any hammer will drive in a nail.”
Pharmaceutical companies have spent billions of dollars to convince consumers that there are differences in their products. They have pushed new versions of such compounds as aspirin, ibuprofen (such as Advil), fenoprofen, indomethacin, phenylbutazone and acetaminophen (such as Tylenol). There is Anacin and Bufferin, which are aspirin with caffeine and antacids added. And Ecotrin, which is aspirin in a special coating. And dozens of others. But Mann and Plummer report that all such remedies have only marginal distinctions, mostly affecting less-than-common ailments.
”Aspirin is the oldest, developed in 1897,” Mann said. ”At low doses, it may counter heart attacks and, perhaps, colon cancer. Moderate over-the-counter doses help with headaches and fevers. High doses of aspirin reduce inflammation, but too much will lead to ringing in your ears, to throwing up, to stomach damage, and can kill you.
”Acetaminophen, in moderate doses, is good for headaches and fever. But, taken a lot, by alcoholics for example, who take it for hangovers, it can affect your liver and may eventually kill you. Ibuprofen, in regular doses, is good for headaches and fever. High doses are good for inflammation and especially good for very severe headache pain.”
Prize-winning theory
Other products, fashioned from fenoprofen, indomethacin and phenylbutazone, will undercut average throbbing-of-the-head and moderate aches and pains as well, Mann said. That`s because-except for acetaminophen, which nobody understands at all-all non-steroidal anti-inflammatory drugs are thought to work the same way.
Although hundreds of scientists have looked into the properties of such drugs, seeking to explain their actions on the human body, it was John Vane, a biochemist running a laboratory at London`s Royal College of Surgeons, who came up with the best theory, for which he shared a Nobel Prize in 1982.
His idea is explained in detail in a chapter of Mann and Plummer`s book called, quoting Vane, ”I think I know how aspirin works. Do you?” It describes how acetylsalicylic acid inhibits the synthesis of prostaglandin, a substance that fosters fever or inflammation and accompanying aches and pains in the human body.
That drew on earlier research into the nature of prostaglandins in the 1920s in a small clinic in Brooklyn where Raphael Kurzrock, a gynecologist, was trying to perform artificial insemination of women, making dozens of attempts, only two of which were successful.
According to a paper by Kurzrock, later published in the journal Proceedings of the Society of Experimental Biology and Medicine, it was discovered that, in a number of cases, ”when 0.5 cc. of semen was injected into the uterine cavity, the semen was promptly expelled. That led to the question: What is the action of human semen upon the human uterus?”
Waxy buildup
In 1930, Kurzrock and an associate, Charles Lieb, a pharmacologist, undertook an experiment. ”Having friends who were professional biochemists,” as Mann and Plummer put it, ”they borrowed a laboratory bench and, after what they called `the usual trials and errors,` found that dripping semen on a little strip of human uterus did indeed make the muscle contract-it twitched.” Possibly, the scientists thought, because it hurt.
Further research, this time using sheep semen, was carried on in the 1930s by Ulf Svante von Euler, a Nobel Prize-winning Swedish biochemist who found that prostaglandins were present throughout the human body, not just in the prostate gland, as previously thought. Later, others discovered that prostaglandins derive from a little-known constituent of the body called arachidonic acid, a buttery substance in cell walls that makes them flexible. ”Without it,” John Vane later noted, referring to a kind of ultimate waxy buildup, ”you simply couldn`t move. You`d be rigid as a candle.”
To avoid that fate, cell walls that are irritated release tiny amounts of arachidonic acid. As Mann and Plummer note, amazing things happen, things too complicated to explain here (especially to readers with hangovers). One of these-the one that leads to inflammation and pain-has to do with the human body`s ability to transmute arachidonic acid into prostaglandins.
The marketers move in
So if that`s the theory, why not just make one product-and let everybody use it?
The answer, Virginia, to use a seasonal form of speech, lies in the spirit of commercial competition. Of finding new ways to make a buck. Of the unspoken marketing assumption that new is better. Of the lengths to which big companies, all pushing the same basic product, will go to share a market worth up to $25 billion a year. Alas, Virginia, there is such a thing as ”greed, business acumen and ongoing marketing genius,” as the authors describe it. The results are canny, crazy, unbridled, sometimes brilliant.
In this densely detailed book, Mann, who is 36, and Plummer, 37, both frequent contributors to The Atlantic magazine, bring considerable drama to the history of analgesics, beginning with the development of aspirin almost a century ago by a scientist at the German firm of Farbenfabriken Bayer.
Theirs is a tale of drug counterfeiters in turn-of-the-century America. Of fierce global battles over copyrights. Of the notorious I.G. Farben conglomerate, the successor to the original developers of aspirin, and its ties to Nazi Germany. Of wild promoters who once hired Eva Peron as an aspirin pitchwoman in Argentina. Of sloganeers on TV (”Nine out of 10 doctors recommend …” and, ”Fast, fast, fast relief”).
”Aspirin makers have a remarkable, perhaps unique, history of competition,” the authors conclude. ”They have been slugging it out over exactly the same ground since the end of the First World War.”
Is new better?
In 1990, Americans bought almost $2.7 billion worth of analgesics, sales that amounted to one-quarter of the over-the-counter drug market, more than the total for shampoos, deodorants, toothpastes or any category of health and beauty products. But lamentably for aspirin-makers, their share of the market has been declining.
”There`s a TV commercial I saw the other day that said, `Aspirin, 1899!
Tylenol, 1954! Advil, today!` ” Mann noted in an interview. ”What`s great is its unspoken assumption, that new is better.”
These days, scientists are looking into aspirin`s unexpected possibilities in perhaps preventing heart attacks, ameliorating senility, decreasing the risk of colon cancer and potentially helping with many other medical conditions. There are few firm conclusions yet, but what they are looking at has been used by humans for a long time.
The roots of aspirin
Aspirin is related to acetanilid, a coal-tar derivative whose properties resemble those of willow bark, which has been used to relieve fever and pain since the time of the ancient Greek physician Hippocrates.
In the 18th Century, Rev. Edward Stone, an English experimenter who believed Providence placed cures for diseases not far from their sources, suggested that people who got fevers from swamps might be cured by trees that grew in swamps. He ground up dried willow bark, mixed it with water and gave it to 50 feverish people. With few exceptions, the fevers went away.
Unfortunately, crushed dried willow bark tasted terrible, a problem addressed by a company Friedrich Bayer and Johann Friedrich Weskott set up in Germany in 1863.
Never short of ideas, they started in the dye business. Its aniline blue dye, for example, called for 48 egg whites in each batch, with left-over yolks going to make pancakes for the workers.
In 1886, the company, taking a beating in the hotly competitive dye field, branched into drugs. Its empire-building director, Friedrich Carl Duisberg Jr., an industrialist whom the authors call ”as much a member of the commercial pantheon as Rockefeller and Rothschild,” set up a drug lab and came up with a process for modifying salicylic acid to produce acetylsalicylic acid. It was, and still is, what we know as aspirin.
Not much else in this voyage to the wilder shores of capitalism is that simple.
For example, take the confusion over ownership of the word ”aspirin.”
In the United States, Britain and France, aspirin is a generic nickname for acetylsalicylic acid. No one owns it. Any company can use it. In Canada, Aspirin is a trademark owned by Sterling-Winthrop Inc. In Germany, and 70 other countries, it is a trademark of Bayer AG. Nor has there been any shortage of dirty tricks or fights over what one brand says about another.
One question unanswered
The authors of this book, both raised in a suburb of Seattle, have known each other since the 7th grade. Plummer, who still lives near Seattle, was a staff economist at the Federal Trade Commission from 1982 to 1986. Mann, who spends most of his time in New York, is a free-lance magazine writer, with credits including Science and Smithsonian magazines.
How much research do they do? ”Let me think,” Mann said. ”I have a filing cabinet with six drawers, each 36 inches wide, all solid with material. Then I have six or seven megabytes of computer stuff. Mark has the same amount-and about half again.”
With all that digging, might one think that this book is the complete and final word on analgesics? Wrong!
The authors failed to mention that no one has ever figured out how to quickly remove the cotton wad from the top of an aspirin bottle.
