On September 22, just days after the release of the CDC report, Procter & Gamble voluntarily removed Rely from the marketplace. And they went a step further: together with the Food and Drug Administration, the company designed a massive ad campaign telling women not to use their product. The campaign, which began October 6, ran on network television and radio and in over 1,200 newspapers nationwide for four weeks. The FDA, meanwhile, urged women to get rid of their existing supplies of Rely, and recalled inventories of the product from stores nationwide.19
Procter & Gamble wouldn’t comment on the cost of the campaign, but it clearly was in the tens of millions of dollars. It was unprecedented. As one FDA official privately put it: “We’re not used to having such strong company cooperation in a product removal case. And we’ve never seen a company volunteer to spend millions of dollars to tell people not to buy their product.†Procter & Gamble, for their part, couldn’t be accused of pure altruism. As company representative Marjorie Bradford put it: “Procter & Gamble makes over eighty-eight consumer brands of household and hygiene products. We must maintain a reputation for safe and effective products.†Bradford didn’t mention the half dozen lawsuits filed by consumers of Rely.
Together with the FDA, the company ran hundreds of market surveys, testing their “do not use our product†ads on women in shopping malls all over America. According to the FDA the ads were 97 percent effective in conveying two messages: don’t use Rely, and avoid use of all tampons until the Toxic Shock mystery is solved.
The “don’t use Rely†campaign was not applauded by all. In their ads Procter & Gamble quoted the CDC as saying, “Women can almost entirely eliminate their risk of TSS by not using tampons. Women who choose to use tampons can reduce their risk by using them intermittently during each menstrual period.†The other manufacturers were outraged, and expected to see their future tampon sales plummet. Tampax took out ads in The New York Times and Washington Star denouncing Rely, and offering their product as a healthy alternative.
The American College of Gynecologists, representing most of the nation’s 23,000 gynecologists, issued a warning to women during the first week of October: avoid using tampons—all tampons.
Quietly, some non-CDC scientists involved in investigations of TSS cases were nervous about the agency’s position on Rely, and tampons generally. As Osterholm put it: “We had a hepatitis A outbreak in Minnesota a few years ago among people who ate hot dogs. We took tough action and moved quickly on the hot dogs. But it turned out the culprit was the relish. You’ve got to be very careful about these associative findings.â€
On October 8 the CDC hastily published the results of a small Utah TSS study that seemed to further implicate Rely.20 The study compared the tampon use patterns of 29 Utah women who developed TSS during 1979–80 with the behavior of 91 age-matched females who did not have TSS. Sixty percent of the TSS cases involved use of Rely, compared with a Rely use rate among controls of only 23 percent.
Ralph Nader’s Health Research Group in Washington, D.C., was not happy. The public advocacy organization, and its lead physician, Dr. Sidney Wolfe, were convinced that the federal government was dragging its feet with the tampon industry, putting the female public at peril. Wolfe attacked part of the message contained in the FDA/Procter & Gamble ads: namely, the statement that “tampons do not cause TSS.â€
“They most certainly do!†Wolfe asserted. Convinced that the CDC’s targeting of Rely was justified, Wolfe charged that the ads produced by Procter & Gamble were unsatisfactory. Though 97 percent of women got the proper messages from the television ads, according to most market surveys, only 89 percent correctly interpreted the company’s print advertisements.
Under pressure from the Health Research Group, the FDA held public hearings on TSS in October, and after listening to a range of testimony from women’s groups, medical and scientific organizations, and the CDC, issued its first set of tampon regulations.
It was the first time any federal agency had sought to regulate tampon safety.
The FDA ordered tampon manufacturers to put instructions inside their product boxes, describing TSS and explaining the healthy, safe ways to use tampons. Though the agency wasn’t certain what “healthy and safe use†might be, there was general agreement that frequent tampon changes—shorter durations of use—were fundamental. The manufacturers were also ordered to list all the ingredients of their tampons and inserters on the product boxes. Also on the outside of the boxes the manufacturers had to list the various available tampon sizes, indicating where on that scale the enclosed devices fit. And the FDA reclassified tampons as Class Three Medical Devices, thus, for the first time, legally requiring premarketing safety tests.
With lawsuits, and the female death toll, mounting, the tampon industry complied without the usual formal corporate protests that typically accompanied escalations in FDA regulation.
Rely tampons had barely been off the market four weeks when Osterholm reported a surge in TSS cases in Minnesota. Reflecting on his earlier study that found that 34 percent of TSS cases had used Rely, Osterholm said the CDC had reached the wrong conclusions in September.
“No other brand showed such a marked difference, so Rely does stand out. But that only accounts for a third of the cases—what about the other two-thirds?†Osterholm said in November. “We say there is risk with all tampons.â€
Describing tampons as an “amplifying factor,†Osterholm added that “when we say tampons are guilty, it could be something correlated with wearing tampons.â€
Todd was also distressed.
“All of our [Denver] cases occurred before Rely got on the market in Colorado,†Todd said. “TSS is not caused by tampons. Absolutely not. What we don’t know about TSS far outweighs what we do know. You can go to a bar and get twelve theories about where TSS came from. I think TSS is a disease in search of a [bacterial] toxin.â€
In response, the CDC’s Schmid said he and the agency were standing by their Rely study. “The timing for the release of that information was very critical. You act as quickly as you can, based on your findings,†he said, noting that Wolfe and other activists were accusing the agency of not moving with adequate haste.
By late November, however, Schmid readily agreed that the focus needed to shift from targeting tampon brands to figuring out what actually caused TSS. And by late December, CDC officials were conceding that “all tampon brands are suspect now,†as well as tampon alternatives, such as sea sponges. Two TSS cases had surfaced during the fall among women who, afraid of getting the disease by using tampons, had switched to the then chic alternative, natural sponges.
Operating on the assumption that the tampon acted as “a growth media,†FDA officials said that leaving a tampon in the vagina for long periods of time “is not helpful.†For the five years prior to the appearance of TSS, the key advertising pitch in the volleys fired by competing manufacturers was aimed at offering ever-longer amounts of “freedom†from concerns about leakage, through the use of higher-absorbency fibers. As a result, women had extended the amount of time they used a single tampon from an estimated range of one to three hours to an average of 6.8 to 7.2 hours, according to the CDC.
Like many local public health officers, Dr. Betty Agee of the Los Angeles County Health Department noted a continuing TSS problem after Rely’s withdrawal from the market. She saw no correlation with the brands women used, but did see “a consistent pattern of use of higher-absorbency tampons.†Sixty percent of the Los Angeles County cases involved not Rely but Playtex superabsorbency tampons, Agee said.
In Connecticut, where Rely was never even sold, there was a sizable incidence of menstrual TSS involving all four of the other tampon brands. And in California, where Rely hit
the market in May 1979, the upward surge in TSS cases began in 1977, coincident, local authorities said, not with a specific brand but with the introduction by all manufacturers of higher-absorbency products.21
There were three possible explanations for the apparent statistical correlation between TSS in women and superabsorbent tampons: like the Rely connection, it could have been a misleading indicator related to some as yet undiscovered underlying mechanism; something inside the new synthetic products could actually promote the growth of Staphylococcus;22 or the superabsorbent products were simply left inside the vagina too long, serving as a sort of petri dish for bacterial growth.23
In early October, Dr. Keith White, director of the American College of Obstetrics and Gynecology, linked TSS to the carboxymethyl cellulose fibers used in some superabsorbent tampons. Such fibers, he asserted, were making the vagina abnormally dry and causing tiny lacerations in the vaginal wall through which Staphylococcus entered the bloodstream. A parallel theory had it that the carboxymethyl cellulose also bolstered the size of the staph population by serving as a chemical source of sugar for the bacterial colonies.24
In the CDC lab, however, Shands was unable to grow staph bacteria on the CMC fiber alone. At the National Institute of Occupational Safety and Health laboratories in Cincinnati scientists showed that the fibers were merely coated with CMC, which acted as a lubricant, probably reducing vaginal irritation. CMC, they noted, was contained in most popular eye drops, and there were no reports of increased conjunctivitis with its use.
In addition, there was a fundamental error in theories that linked fiber-induced lacerations to TSS: the bacteria didn’t need to enter the bloodstream to produce TSS. In fact, if the bacteria did get into the bloodstream, a different disease resulted: septicemia. Toxic Shock Syndrome was produced when the bacteria colonized a mucosal area and secreted deadly toxins. The toxins were tiny molecules that could readily make their way into the bloodstream in the absence of cuts, scratches, ulcerations, or other injuries to the vaginal wall. If the fiber-cut/bloodstream theory of the disease were correct, the result would have been a very different disease.
As 1980 came to a close the Wisconsin group surveyed its TSS cases, all but two of which involved menstruating females who took ill after January 1979. They found that S. aureus could be cultured from the vaginal discharges of three-quarters of women with TSS,25 but only from 2.6 percent of randomly selected healthy women who attended a Wisconsin family planning clinic.26
“If a new strain of Staph. aureus with the potential to produce an unidentified toxin has evolved, it seems likely that conditions in the vaginas of some menstruating women who are using tampons enhance growth of the organism, production of the toxin, or absorption of the toxin,†the Wisconsin group wrote.
By January 30, 1981, the CDC was exultant, claiming there had been a marked reduction in TSS cases, from a high of 119 cases reported in August to 37 in December. The agency credited their swift action against Rely for bringing the epidemic under control.
But overall statistics offered a less sanguine picture. Between January 1975 and October 1980 a total of 408 TSS cases, with 40 deaths, were reported. By January 30, 1981, the total had reached 941 cases and 73 deaths. Critics charged that publicity surrounding Rely had contributed to an apparent decline in late November/early December cases, but Rely’s withdrawal from the market was just a blip on the social radar screen. The real story, they argued, was that frightened women turned away from tampons—all tampons—in record numbers. Tampax reported a 25 percent drop in sales for the eight weeks following the massive Rely/FDA ad campaign, and other tampon manufacturers noted sales declines that ranged from 15 to 25 percent.
“Removal of Rely was clearly wrong,†Todd said in January.27 “If I were Procter & Gamble, I’d sue FDA for $75 million!â€
Behind the scenes a bitter feud was raging between scientists in and out of the CDC over what precisely was the connection between tampons, S. aureus, and Toxic Shock Syndrome. Publicly CDC officials projected confidence in their position on Rely. But privately there was far less certainty.28
“The only thing we know is that tampons soaked in blood support bacterial growth,†the CDC’s Shands said. Privately, the CDC’s Dan acknowledged that the strain of Staphylococcus responsible for menstrually related TSS appeared to be new. And he admitted that there might well be evidence to support the assertions of a maverick UCLA scientist, Patrick Schlievert, that the new staph strain produced a lethal toxin, unlike any that had previously been discovered in the bacteria.
But publicly the CDC scientists, as well as Jim Todd, denounced immunologist Schlievert, accusing him of weaving bizarre theories in public view, failing to publish his work in refereed scientific journals, and seeking the media spotlight for personal glory. In the Midwest, however, where TSS was taking its greatest toll, Schlievert’s theories were considered right on the money, so much so that Minnesota collaborators would soon woo the immunologist away from sunny California, convincing him to take a post at the University of Minnesota Medical School in 1982.
Schlievert got onto TSS research two years before the CDC’s January 1980 announcement of the existence of the new ailment. A Pennsylvania physician was handling an odd case of what seemed to be Kawasaki syndrome, or perhaps scarlet fever, and needed help. He sent the patient’s blood samples to Schlievert in Los Angeles. The immunologist isolated a previously unidentified streptococcal poison from the patient’s blood, dubbing the substance “pyrogenic exotoxin,†meaning fever-producing poison secreted by a bacterium.29
Convinced that he might have stumbled upon the molecular cause of both scarlet fever and Kawasaki syndrome, Schlievert set to work testing the effect of pyrogenic exotoxin on mice and rabbits.30
While the CDC was preparing to move against Procter & Gamble’s Rely tampons, Schlievert was busy isolating pyrogenic exotoxin from TSS patients’ blood and mucosal samples, sent to him from Minnesota by Osterholm. He quickly confirmed the presence of the toxin, and warned Osterholm that pursuit of a tampon connection, though there probably was one, was diverting attention from the real issue: staphylococcal poison. Using Los Angeles samples sent to his lab by Agee, Schlievert confirmed the presence of pyrogenic exotoxin there as well.
CDC scientists were openly skeptical. While agreeing with Schlievert’s assertion that the TSS staph strain was making some new, or usually extremely rare, toxin, Bruce Dan and Kathryn Shands were less than thrilled about discovery of pyrogenic exotoxin.
“More work needs to be done to prove that Schlievert’s candidate is the actual toxin,†Shands said. There were, she said, several candidates for the TSS toxin.
Schlievert, who was a young, aggressive academic scientist, responded with the kind of certitude that was often misinterpreted as arrogance. “I’m already beyond the stage of trying to figure out what causes the disease,†he said. “I don’t care what the CDC says.â€
Having isolated the toxin and shown that it produced disease in animals, Schlievert set out to prove Koch’s Postulate. Named after 1905 Nobel laureate Robert Koch, the Postulate was a statement of the experimental evidence required to establish the causal relationship between a given microbe and a particular disease. To prove that an organism or agent actually caused a disease, Koch (who discovered the cause of tuberculosis) said a scientist had to identify the presence of the agent in every case of the disease; isolate the organism and grow it (or its toxin) in the laboratory; show that the laboratory-grown sample caused the disease when it was injected into animals; and then re-isolate the organism, or toxin, from the ailing laboratory animals.
Schlievert isolated toxin from TSS patients and injected it into rabbits. Within a matter of hours the rabbits developed classic Toxic Shock Syndrome, complete with high fevers, markedly low blood pressure, and mucosal secretion of S. aureus. He was then a
ble to re-isolate the toxin from the rabbits’ infected mucosa. Two weeks later Schlievert gave the by then recovered rabbits a subcutaneous second injection of the toxin. Half the animals developed scarlet fever-like rashes.
When Schlievert measured various components of the immune systems of the rabbits, he found that T-cell levels jumped following the first toxin injections. Four days after the injection, with the animals still ailing, their antibody production levels (particularly of IgM) were way down, while their total white blood cell counts were two and a half times above normal. It seemed that suppressor T cells, which were in astonishing abundance, were stifling the rabbits’ antibody responses.
By day ten, the toxin had killed off most of the rabbits’ T cells, and Schlievert saw a surge in the antibody-producing B-cell population. In particular, IgG antibodies filled the bloodstream, where they sought out their toxin targets. By day twelve the rabbits’ blood was full of tightly bound complexes of these antibodies coupled with the toxin molecules—some of which were still attached to the T cells they had invaded.
The immune system then became confused, Schlievert said. It saw the T cells, as well as the toxin, as its enemy and began to autodestruct. The result was autoimmune disease.
On the basis of what he saw in rabbits and mice, Schlievert put forward the following hypothesis of the human disease: a new form of S. aureus was in the United States (and, based on case reports, by 1981 in Sweden and Canada); the strain possessed a set of genes that coded for pyrogenic exotoxin A; first-time infection resulted in a mild form of flu-like disease that did not meet the CDC definition of either TSS or Kawasaki syndrome; that first exposure did, however, set in motion a chain of events in the immune system that sensitized the patient; following a second or third round of exposure to the Staphylococcus toxin the individual’s immune system went into a self-destruct mode, and the unchallenged toxin produced Toxic Shock Syndrome.
The Coming Plague Page 62