Except for the president of the United States, the toughest job in Washington, D.C., may belong to the commissioner of the Food and Drug Administration. This agency routinely makes decisions that directly affect the health of millions of people. The acceptance or rejection of just one new drug application can influence hundreds of millions of dollars that flow -- or do not flow -- from the pockets of consumers into the coffers of the pharmaceutical industry.
Few passions are more intense (and not necessarily reasonable) than those of frightened people who believe that they may be denied a medicine that they hope might save them or have been given a drug that might kill them. Add to this mix the calculated pressures from a corps of shrewd industry lobbyists who have showered enough cash on Congress and the administration in power to ensure an unholy legion of allies. Stir in ideological preconceptions such as "regulation is bad and strangles innovation" or "drug companies are crooks that exploit the sick." Open this all up to the media spotlight and the result is decision-making under the most challenging of circumstances. (When it took President Clinton nearly three years to replace Commissioner David A. Kessler, the wags explained it was hard to find someone crazy enough take the job but expert enough not to be a danger to him or herself and others in this pivotal office.)
Agency leadership over the last century is one focus of New York Times reporter Philip J. Hilts' new history of food and drug regulation, "Protecting America's Health." He begins with the nation's first food and drug czar, Indiana physician Harvey Wiley, and ends with the FDA's new commissioner, Mark B. McClellan. Hilts has his work cut out for him, given the FDA's wide-ranging responsibility for foods (except meat), drugs, biological products, vaccines, the blood supply, medical devices, microwave appliances and dietary supplements. His result resembles the agency he writes about: substantial strengths mixed with unfortunate weaknesses.
Hilts' primary mission is to document, explain and promote the benefits of food and drug safety regulation. Early on, he identifies his target: "Recently a rump movement in America, led by hard conservatives, has been reviling the consumer protection agencies and refusing to accept science as the basis of policy."
He is referring to the 1990s when the FDA lay squarely in the crosshairs of Newt Gingrich's neoconservative revolution, and he provides point-by-point rebuttals of many of the dubious allegations and outright falsehoods that were claimed to justify deregulation of food and drugs. He approvingly reports that the drive largely, but not entirely, failed. Ultimately, however, Hilts' book makes it clear that while the agency has been led by both vigorous regulators and apologists for industry, its usefulness is ultimately defined by the powers that Congress grants it. Two pivotal moments of legislative history, both covered extensively in the book, demonstrate this point.
In early 1962, Sen. Estes Kefauver, a Tennessee populist, was near failure in a long legislative campaign to strengthen the FDA's authority to deal with the growing powers of the pharmaceutical industry. Since World War II, antibiotics, steroids, polio vaccine and other breakthroughs had revolutionized industry and medicine, but the FDA's procedures and authority had changed little since 1932. Although three years of hearings had exposed industry profiteering, unsavory marketing and an FDA that was often too cozy with industry, Kefauver had not gotten support from the Kennedy White House.
Then, suddenly, the public learned that powerful new drugs could harm as well as heal. Magazines and newspapers around the world published heart-rending pictures of horribly deformed babies, the result of pregnant women taking a new sedative called thalidomide. Although the consequences were largely avoided in the United States because the FDA delayed the drug's marketing until the manufacturer could provide more scientific data, the pictures quickly reversed the political tide. A tough law was quickly written and speedily passed.
Congress declared that a prescription drug could not be marketed unless the manufacturer could demonstrate with "substantial" scientific evidence that it was effective. (A law requiring evidence of safety was already on the books.) Furthermore, the law admitted a single proof of efficacy: controlled clinical trials. It was a revolutionary idea, especially the requirement for controlled clinical trials. For the first time, the law rejected testimonials from patients who swore that they had been miraculously cured, and it ignored the expert opinions of doctors who history instructs us are remarkably uncritical about the treatments they prescribe. Nor did it accept long traditions of use, whether for decades or for centuries.
To require scientific evidence of efficacy also meant that every drug had to undergo -- in the process of the clinical trials -- substantial systematic testing involving hundreds to thousands of patients. This made it possible to identify risks that otherwise might not have been observed. Drugs became more expensive, but the frauds and poisons were weeded out.
The second legislative revolution came in 1994, and it remains a great embarrassment to the country. For decades, vitamins, minerals, some human hormones and herbal products had existed in a regulatory never-never land. These products, called dietary supplements, were not exactly foods, whose requirements are quite simple and involve purity, labeling and freedom from contamination. Nor were they exactly drugs, which must meet the strict scientific standards described above.
When a contaminated dietary supplement called L-tryptophan caused more than 1,500 cases of injury and 35 reported deaths, the FDA began to consider strengthening the regulation of these products. This in turn triggered a massive political reaction. Some makers of vitamins and herbal products persuaded their loyal adherents that the FDA was threatening to make these products available only by prescription. An avalanche of constituent mail persuaded a frightened Congress to exempt these products from meeting basic safety standards. The result is succinctly summarized by a recent FDA statement on L-tryptophan: "The manufacturer is responsible for insuring that its products are safe. [The manufacturer] is not required to obtain pre-market review or approval from the FDA. Moreover the firm is not required to submit scientific evidence to the FDA of the safety of its products or ingredients."
At one point, the agency had more full-time employees monitoring the safety of drugs for pets and farm animals than checking on dietary supplements taken by tens of millions of people, but the primary blame for the lack of safeguards lies in the flawed dietary supplements law. It is not a failing of the agency, which was rebuffed in its efforts to protect the public health.
Many of the strengths and weaknesses of "Protecting America's Health" come from its being a reprise of a surprisingly large number of the events that have made headline news in food and drug regulation over the last century. But to cover so much ground quickly (the gift and bane of the newspaper reporter's craft), Hilts has often condensed the existing major works on the subject and seldom gone beyond them. We see the world of 1906 through the eyes of Wiley, the first food and drug czar, in part because he has left us two vivid memoirs. Hilts' case study of the deaths linked to an antibiotic called chloramphenicol is mostly a rewrite of Thomas Maeder's excellent book, "Adverse Reactions." Similarly, his chapter about the birth of the 1962 act owes much to Richard Harris' gripping and detailed "The Real Voice." The account of the disaster involving drugs for irregular heartbeats is taken from and attributed to my book, "Deadly Medicine," and two chapters draw heavily on David Willman's spectacular Pulitzer Prize-winning series in the Los Angeles Times in 2000, "Seven Deadly Drugs."
Also, Hilts' prose suffers by comparison to the vivid writing that characterized many of his secondary source books and articles. An example is this graceless and inaccurate sentence that comes at the end of a paragraph about a flu treatment called Relenza, which the FDA approved in 1999 despite extremely weak evidence of benefits. He writes: "Besides Relenza, Glaxo was responsible for three drugs withdrawn from the market because of death and injury in the past four years: Raxar, Lotronex, Hismanal, and with Bayer as distributor, Baycol."
Hilts writes "three drugs withdrawn" and then lists four drugs. Also, Johnson & Johnson (not Glaxo) manufactured and withdrew Hismanal, and in the case of Baycol, Bayer was the manufacturer and responsible for its clinical testing and its safety withdrawal; Glaxo marketed it in some countries. Meanwhile, Lotronex, a drug for irritable bowel syndrome, was returned to the market (likely after this book was already set in type). In doing so, the FDA ignored every one of the new safety precautions that its advisory committee on drug safety had recommended and instead accepted Glaxo's plan.
Hilts closes "Protecting America's Health" by tentatively suggesting that, "after the conservative storm, the FDA was back to steering a more usual course." I am not so sure. But I fully support his judgment that the FDA, despite its flaws, plays an essential role in protecting health. Anyone prone to sneer at "government bureaucrats" should visit the FDA and meet some of the doctors and scientists who bring great expertise and a commitment to public service to bear on some of the most daunting safety issues in our society.