BOOKS OCTOBER 19, 2013
Not long ago, I cared for a middle-aged attorney who had a sarcoma. This kind of cancer arises from connective tissues like muscle and bone; if confined, it usually can be cured. But in this woman’s case, the malignancy was discovered after it had spread from her thigh to her lungs and liver. She initially was treated with chemotherapy, and the tumors shrank; but a year later, they grew again.
My patient told me that she was a clear-eyed and rational person who made decisions based on facts: she would do so about her treatment, much the way she did in her practice as a lawyer. She underwent a series of increasingly arduous therapies, but her condition worsened as the cancer grew in vital organs, and she felt increasingly desperate. Friends, with what she acknowledged as good intentions, sent her reports from the Internet of “cancer cures,” which included cleansing her body of toxins with coffee enemas, ingesting solutions made from Chinese herbs, passing her plasma over resins. At one of our last appointments, my patient recounted how hard it was not to give in and chase illusory treatments. “I so much want to live,” she said.
Typically absent from the claims about many “alternative treatments” are their risks. The significant harms that they can pose form the fabric of Paul Offit’s important and timely book. Offit writes in a lucid and flowing style, and grounds a wealth of information within forceful and vivid narratives. This makes his argument—that we should be guided by science—accessible to a wide audience.
Although conventional therapies can be disappointing, alternative therapies shouldn’t be given a free pass.... All therapies should be held to the same high standard of proof; otherwise we’ll continue to be hoodwinked by healers who ask us to believe in them rather than in the science that fails to support their claims. And it’ll happen when we’re most vulnerable, most willing to spend whatever it takes for the promise of a cure.
Offit is a pugilist in the battle against charlatanism, and he lands punch after punch with hard facts about harms.
The possibility of harm caused by natural products ... isn’t theoretical. Blue cohosh can cause heart failure; nutmeg can cause hallucinations; comfrey, kava, chaparral, Crotalaria, Senecio, jin bu huan, Usnea lichen, and valerian can cause hepatitis; monkshood and plantain can cause heart arrhythmias; wormwood can cause seizures; stevia leaves can decrease fertility; concentrated green tea extracts can damage the liver; milkweed seed oil and bitter orange (Citrus aurantium) can cause heart damage; thujone can cause neurological damage; and concentrated garlic can cause bleeding....And it’s not just the supplements themselves that might be harmful, but what’s contaminating them. In 2004, researchers at Harvard Medical School tested Indian (Ayurvedic) remedies obtained from shops near Boston’s City Hall. They found that 20 percent contained potentially harmful levels of lead, mercury, and arsenic....1
These problems aren’t rare. Between 1983 and 2004, poison-control centers in the United States received 1.3 million reports of adverse reactions to vitamins, minerals, and dietary supplements, of which 175,268 required treatment in hospitals and 139 resulted in death. In 2012, the FDA [Food and Drug Administration] estimated that approximately 50,000 adverse reactions to supplements occurred every year.
A pediatrician expert in infectious diseases, Offit is particularly focused on vulnerable children, who do not have the agency to make choices for themselves. In such instances, deluded parents can prevent a child with a potentially curable malignancy from receiving proven therapies, while pursuing remedies that are not only nonsensical but also noxious. Early in the book we are introduced to Joey Hofbauer, a seven-year-old who, in 1977, developed a lump in his neck. He soon received a diagnosis of Hodgkin’s disease; his prognosis was excellent, with a 95 percent chance of complete remission: “Joey could live a long and fruitful life. But for Joey Hofbauer, the road to recovery wasn’t going to be easy.” The barriers in his path were not a lack of insurance or of access to expert oncologists. Rather, his parents, John and Mary Hofbauer, believed that there must be a more “natural” way to cure their son than toxic chemotherapy and radiation. They decamped to the Fairfield Medical Center in Montego Bay, Jamaica, to receive laetrile, a touted cancer “cure” extracted from apricot pits.
Typically absent from the claims about many “alternative treatments” are their risks.
The state of New York tried to take custody of Joey, and a legal battle ensued. While the dispute raged, John Hofbauer secretly gave Joey several doses of laetrile. To the dismay of the state’s Child Services, Judge Loren N. Brown of the Saratoga Family Court agreed to allow the Hofbauers to treat Joey with laetrile for six months, so long as they identified a licensed physician willing to administer it. The parents found Michael Schachter, a psychiatrist from Nyack, New York. As Offit recounts, Schachter had them sign a consent form releasing him of all responsibilities, and it included the statement that he was not a cancer specialist and had no direct experience with orthodox cancer-therapy modalities of chemotherapy, radiation, or surgery, and was not in a position to advise the Hofbauers about the benefits and risks of treatments for the malignancy. But despite these limitations, Schachter was not averse to assuming care and providing laetrile—along with “raw milk, raw liver juice, cod liver oil, soft-boiled eggs, Staphylococcus phage lysate (staph bacteria infected with a virus), pancreatic enzyme enemas (which partially dissolve the lining of the colon), massive doses of vitamin A (which cause blurred vision, bone pain, and dizziness), a vaccine to prevent ‘Progenitor cyrptocides’ (a bacterium believed by a physician named Virginia Livingston to cause all cancers), a vegetarian diet, daily coffee enemas made by adding three heaping tablespoons of regular coffee to one quart of water (coffee enemas had already caused two deaths), seven injections of an ‘autogenous vaccine’ (made from bacteria in Joey’s urine), and Wobe-Mugos enzymes (a combination of several pancreatic enzymes obtained from pigs).”
At the end of six months, several oncologists testified before Judge Brown that the cancer had grown in its original location and spread to other parts of Joey’s body. Offit notes that “Schachter apparently didn’t realize that Joey’s ‘occasional nausea and abdominal cramps’ were probably caused by cyanide poisoning from large doses of laetrile, having never obtained blood cyanide levels to check it out.” Despite all the evidence that the cancer was advancing, Schachter contended that his therapies were succeeding. Judge Brown ruled in favor of the parents, contending that they were “concerned and loving” and that Dr. Schachter was “duly licensed.”
There were formidable allies who supported the Hofbauers, among them the John Birch Society, intent on eliminating government oversight. The Birch Society founded the Committee for Freedom of Choice in Cancer Therapy. Such groups had great sway in the laetrile debate: in 1976, Alaska legalized the manufacture and sale of the extract from apricot pits and, by 1979, twenty-one states had followed.
The Saratoga County Department of Social Services appealed to higher courts but failed to have the decision about Joey Hofbauer reversed. In July 1980, at the age of ten, the boy died of Hodgkin’s disease, his body riddled with the lymphoma. Four months later, the actor Steve McQueen died of an aggressive type of lung cancer, called mesothelioma; he had left Cedars-Sinai Hospital in Los Angeles and gone to receive laetrile in a clinic in Mexico. A year later Charles Moertel, an oncologist at the Mayo Clinic, led a multi-center clinical trial of 178 patients with advanced cancer, testing laetrile and high doses of vitamins. There was no sign of benefit, and several of the patients suffered symptoms of cyanide poisoning from the treatment. In 1987, the FDA banned the sale of laetrile.
Despite the discrediting of laetrile, and other fallacious cancer therapies such as shark cartilage, surveys show that more than 50 percent of Americans look to so-called “alternative” therapies for serious diseases as well as to ameliorate the effects of aging. In the United States, alternative medicine is a “$34-billion-a-year business.” It is a lucrative and thriving enterprise, and some of its most prominent promoters have prestigious pedigrees from schools such as Harvard, Yale, and Columbia.2 The public assumes that someone educated in such institutions, where critical thinking and scientific rigor are prized, must be a reliable guide through the thicket of illness. Yet this clearly is not the case. Before Offit, others have discredited claims by gurus with Ivy League diplomas such as Andrew Weil (Arnold Relman in The New Republic) and Mehmet Oz (Michael Specter in The New Yorker). Offit extends these critiques by, in essence, taking the reader on rounds, where clinical presentations are examined for gaps in data and flaws in thinking:
In February 2011, Mehmet Oz asked Dr. Issam Nemeh onto his show. Nemeh is a faith healer. He believes that people can be cured with prayer. One of Nemeh’s successes, a woman named Cathy, told her story. “I was so sick,” she recalls. “I was coughing up blood. I wasn’t breathing well. I had a mass in my left lung.” Oz showed the audience Cathy’s CT scan, which revealed a small, worrisome mass. The diagnosis had been lung cancer. “I went to see Dr. Nemeh,” Cathy continued. “And I had a two-hour visit where we talked and we prayed together. All of a sudden I took this deep breath of air. And I just kept taking breaths. I couldn’t believe how much air I was taking in. I felt wonderful.” Just like that, Cathy’s mass was gone. A second CT scan proved that her lungs were back to normal. No chemotherapy. No radiation. Just prayer. A miracle.
Unfortunately, Cathy’s story contained several inconsistencies. First, Oz never mentioned a biopsy, suggesting instead that the diagnosis had been made by CT scan alone. This should never happen. Because infections can mimic cancer—and because infections are treated differently—a biopsy is required. Second, a closer look at Cathy’s CT scan showed that the mass had ragged edges, more consistent with inflammation (seen in bacterial infections) than cancer (where edges are typically smooth). In all likelihood, Cathy had a minor case of bacterial pneumonia that resolved without antibiotics, a common event. Oz’s viewers, however, were left with the notion that prayer alone had cured her.
A powerful libertarian streak runs through American culture. In its more sober form, this political perspective argues that adults are free to choose what they want for themselves, and government should not intrude in their health decisions. At the fringe, some libertarians are conspiracy theorists who contend that your doctor and your government don’t want you to have access to miraculous alternative medicines, because that would reduce their incomes and limit their control over your life. But since the writings of the muckrakers at the beginning of the twentieth century, notably Upton Sinclair in The Jungle, the federal government has regulated food and medicines. Society has largely understood that consumers should be protected against nefarious advertising and potentially harmful products. Offit aptly quotes Isaiah Berlin on the need for limits to the libertarian creed: “Liberty for the wolves is death for the lambs.”
Those limits were ultimately imposed by the FDA regarding laetrile, but for many other treatments, such as supplements and megavitamins, Offit recounts a sad history of congressional inaction.
Despite a wealth of scientific evidence, most Americans don’t know that megavitamins are unsafe. So why don’t more people know about this? And why hasn’t the FDA sounded an alarm? The answer is predictable: money and politics....
In December 1972, the FDA announced its plan to regulate vitamins containing more than 150 percent of the recommended amount; those containing larger quantities would require proof of safety before sale. Vitamin makers saw this as a threat to their $700 million-a-year business. Represented by the National Health Federation (NHF), the industry set out to destroy the bill. In the end, it did far more than that....
In 1975, William Proxmire introduced a bill banning the FDA from regulating megavitamins. Bob Dole, William Fulbright, Barry Goldwater, Hubert Humphrey, George McGovern, and Sam Nunn were cosponsors.
Offit recounts a second attempt at sound regulation.
On June 7, 1991, Henry Waxman introduced the Food, Drug, Cosmetic, and Device Enforcement Amendments, which “authorized any district court to order the recall of a food, drug, device, or cosmetic which is in violation of the [law] if the violation involves fraud or presents a significant risk to human or animal health.” The word most important to Waxman and Kessler [the FDA commissioner]—and that most frightened the supplement industry—was fraud. The FDA knew that claims of safety and effectiveness by supplement manufacturers were either unsubstantiated or wrong; it wanted to protect the consumer by making the industry prove it. Otherwise, the American public would continue to be hoodwinked. But Waxman and Kessler had leaned into a left hook. By taking on a wealthy, powerful, politically connected industry, they not only didn’t get what they’d wanted; they got the opposite of what they’d wanted. “Kessler wanted to drive a stake into the heart of the dietary supplement industry,” recalled Peter Barton Hutt. “Instead, he drove it into the heart of the FDA.”
It is ironic that recently the nation was riveted by an outbreak of fungal meningitis in patients who received spinal injections of contaminated corticosteroids, but still embraces representatives who neuter bills introduced in Congress to oversee supplements that can be contaminated with dangerous metals such as lead and mercury. Offit explains why certain powerful legislators give a free ride to “alternative” treatments.
Orrin Hatch loved the supplement industry. As a young man, he sold vitamins and supplements; as an older one, he took them every day—including saw palmetto, to shrink his prostate. “I really believe in them,” he said. “I use them daily. They make me feel better, as they make millions of Americans feel better. And I hope they give me that little added edge as we work around here.”
In turn, the supplement industry loved Orrin Hatch. Four of the industry’s top thirty manufacturers—Weider, Nutraceutical Corporation, Nature’s Way, and Nu Skin International—were located in Utah. (It was the only state with its own supplement trade association: the Utah Natural Products Alliance.) ... Utah benefited from several billion dollars in profits from supplement sales. Hatch’s campaigns also benefited.... Between 1989 and 1994 Herbalife International gave Hatch $49,250; MetaboLife, $31,500; and Rexall Sundown, Nu Skin International, and Starlight International a total of $88,550. In addition, according to his financial disclosures for 2003, Hatch owned 35,621 shares of Pharmics, a Utah-based nutritional supplement company. In the early 1990s, Hatch’s son Scott began working for lobbying groups representing vitamin and supplement makers. Kevin McGuiness, Hatch’s former chief of staff, was also a lobbyist for the industry.
But there is a larger lesson here, one for us in the medical establishment, and I wish that Offit had addressed it. The failure of the FDA to regulate natural products appropriately can be attributed not only to the actions of powerful senators such as Orrin Hatch of Utah and Tom Harkin of Iowa, but also to prominent physicians and scientists who stumble in rebutting their agendas. Dr. David Kessler, as commissioner of the FDA, was grilled by Hatch during Senate hearings about regulation of the supplement industry. Offit excerpts key testimony from that hearing.
HATCH: What safety hazard was the FDA addressing that warranted such intensive use of agency resources and personnel?
KESSLER: Senator, I can read you the claims made for oil of evening primrose. The list starts with cancer.
Kessler refers to a lack of efficacy but never pushes back at Hatch by enumerating the dangers that unregulated products pose to the public, the dangers that fill the pages of Offit’s book.
Offit devotes a chapter to the controversy around the diagnosis and the treatment of Lyme disease.3 In the wake of the discovery of this bacterial infection transmitted by ticks, a cadre of physicians who call themselves “Lyme Literate” arose, contending that people with prolonged fatigue, headache, muscle aches, and other problems were suffering from chronic infection that needed to be treated with prolonged periods of antibiotics. There are no rigorous scientific data supporting such extended treatment. Antibiotics are not benign drugs, and chronic administration can lead to colitis and other severe and debilitating side effects.
In 1993, the Centers for Disease Control, in conjunction with the New Jersey Department of Health, investigated an unusual outbreak in Monmouth and Ocean counties. Twenty-five people, mostly young girls, had had their gallbladders removed. All had been treated for months to years with intravenous ceftriaxone, an antibiotic known to cause gallstones. Although Lyme Literate doctors had diagnosed chronic Lyme, most of these children didn’t have any evidence of Lyme infection. Patients given long-term antibiotics for chronic Lyme have also suffered antibiotic-resistant bacterial infections, severe allergic reactions, and bone-marrow suppression.
The costs of administering such lengthy antibiotic treatments are not small, and so the profits that can be made are substantial. Offit presents the Lyme Literate group as fringe physicians exploiting vulnerable people. He then targets Richard Blumenthal, who, as the attorney general of the state of Connecticut, investigated the Infectious Diseases Society of America (IDSA) after it came out with guidelines asserting the lack of scientific evidence for the existence of chronic Lyme disease and the dangers of prolonged antibiotic therapy. Blumenthal contended that the idsa had conflicts of interest among the panel members who formulated the guidelines, and that to assure consumer protection, there needed to be transparency. Offit depicts Blumenthal (who is now a senator for Connecticut) as in thrall to alternative medical practitioners and a willing tool to further their claims.
Blumenthal was a lawyer. He knew that if the law was on your side, you argued the law (the law wasn’t on his side); if the facts were on your side, you argued the facts (IDSA guidelines were based on more than four hundred scientific studies); and if neither was on your side, you attacked the witness. So Blumenthal attacked the witness, claiming that five of the fourteen scientists who had drafted the IDSA guidelines hadn’t disclosed financial relationships with drug and diagnostic companies. Given that the IDSA had recommended against unnecessary tests and treatments, Blumenthal’s logic was hard to fathom. If followed, the IDSA guidelines would generate less revenue for drug and diagnostic companies, not more.
I was surprised by the portrayal of Blumenthal in the chapter, in part because he has taken principled stands in the gun debate, and also because his brother, David Blumenthal, was a prominent physician at Harvard Medical School, worked in the Obama administration on health-care reform, and is now president of the Commonwealth Fund. (Dr. Blumenthal and I trained together as residents at the Massachusetts General Hospital.) Moreover, John Kraemer and Lawrence Gostin of the O’Neil Institute for National and Global Health Law at Georgetown University noted in an article in Journal of the American Medical Association that a committee representing chronic Lyme advocates released alternative guidelines, and did not disclose important potential conflicts of interest.
Blumenthal and the IDSA reached a settlement. Its terms had the medical society convene another panel of experts, disclose all potential conflicts of interest, take testimony from advocates of chronic Lyme, and then come up with a new set of guidelines. In the end, science prevailed. The recommendations from the idsa were unchanged, because there were no compelling data to support the existence of chronic Lyme disease or for prolonged antibiotic treatment.
Here is another example of how we in the medical establishment could do a better job in informing the public and making the case for science. The lack of transparency with regard to conflicts of interest provides fertile ground for those seeking to discredit sound recommendations. The summary of the settlement with the IDSA includes details that Offit omits from his narrative: a panel member who favored the idea of chronic Lyme disease had been taken off an earlier committee; in addition to undisclosed financial relationships between panel members and drug companies were undisclosed ties to insurance companies. This is relevant because the primary flashpoint was the reluctance of insurers to reimburse treatments that were not endorsed by the IDSA panel.
Physicians and researchers who formulate clinical guidelines need to be bulletproof, that is, fully transparent with regard to any potential conflicts of interest. Recently the Institute of Medicine of the National Academies criticized many expert guidelines for their lack of transparency and failure to hear testimony from patients.4 We should be as demanding of ourselves as we are of those who challenge us.
A scientist approaches all treatments with an open but skeptical mind. Offit lists well-known drugs that originally were obtained from plants, such as digitalis for heart disease, extracted from foxglove. In my own field, one of the most potent therapies for acute promyelocytic leukemia, a particularly vicious form of the disease, is a potential poison, called arsenic trioxide. The discovery of this therapy traces back to stunning tales of leukemia cures from extracts of certain rocks given by shamans in the Harbin region in northern China, investigated in the 1970s. Two decades later, academic physicians, led by Dr. Zhu Chen of the Shanghai Institute of Hematology, investigated these anecdotes and, through arduous laboratory experiments, verified the arsenic compound as the active agent. Arsenic trioxide then was tested for safety and efficacy in rigorous clinical trials. It can have serious side effects on the heart, nervous system, and gastrointestinal tract, so it must be manufactured in a meticulous way with tight quality controls. But it proved to change the trajectory of this type of leukemia, typically fatal in a few weeks, into a frequently curable disease.5 Arsenic trioxide was approved by the FDA, with a long list of significant toxicities to alert the doctor and patient. In April 2010, Chen and colleagues published an elegant paper in Science showing how arsenic trioxide works: it blocks an abnormal protein that drives growth of this leukemia. It is not magic.
Jerome Groopman is the Dina and Raphael Recanati Chair of Medicine at Harvard Medical School and the author, with Pamela Hartzband, of Your Medical Mind: How to Decide What Is Right for You (Penguin).