The Rise and Fall of Laetrile

Laetrile is the trade name for laevo-mandelonitrile-beta-glucuronoside, a substance allegedly synthesized by Ernst T. Krebs, Jr., and registered with the U.S. Patent Office for the treatment of "disorders of intestinal fermentation." This compound is chemically related to amygdalin, a substance found naturally in the pits of apricots and various other fruits. Most proponents of Laetrile for the treatment of cancer use the terms "Laetrile" and amygdalin interchangeably.

It was tried as an anticancer agent in Germany in 1892, but was discarded as ineffective and too toxic for that purpose. During the early 1950s, Ernst T. Krebs, Sr., M.D., and his son Ernst, Jr., began using a "purified" form of amygdalin to treat cancer patients. Since that time scientists have tested substances called "Laetrile" in more than 20 animal tumor models as well as in humans and found no benefit either alone or together with other substances. Along the way its proponents have varied their claims about Laetrile's origin, chemical structure, mechanism of action, and therapeutic effects . Its place in history is assured, however, as a focus of political activities intended to abolish the laws protecting Americans from quackery.

Krebs, Sr.—Laetrile's "grandfather"—worked as a pharmacist before attending the San Francisco College of Physicians and Surgeons, from which he received his medical degree in 1903. During the influenza pandemic of 1918, he apparently became convinced that an old Indian remedy made from parsley was effective against the flu. He set up the Balsamea Company in San Francisco to market the remedy as Syrup Leptinol, which he claimed was effective against asthma, whooping cough, tuberculosis and pneumonia as well. During the early 1920s, supplies of Syrup Leptinol were seized by the FDA on charges that these claims were false and fraudulent. During the 1940s, Krebs, Sr., promoted Mutagen, an enzyme mixture containing chymotrypsin, which he claimed was effective against cancer. He and his son also patented and promoted "pangamic acid" (later called "vitamin B15"), which they claimed was effective against heart disease, cancer, and several other serious ailments. Krebs, Sr., died in 1970 at the age of 94.

Ernst T. Krebs, Jr.—Laetrile's "father"—has often been referred to as "Dr. Krebs" although he has no accredited doctoral degree. He attended Hahnemann Medical College in Philadelphia from 1938 to 1941, but was expelled after repeating his freshman year and failing his sophomore year .

After taking courses in five different colleges and achieving low or failing grades in his science courses, he finally received a bachelor of arts degree from the University of Illinois in 1942 . In 1973, after giving a 1-hour lecture on Laetrile, he obtained a "Doctor of Science" degree from American Christian College, a small, now-defunct Bible college in Tulsa, Oklahoma. The school, founded by evangelist Billy James Hargis, had no science department and lacked authority from Oklahoma to grant any doctoral degrees.

Laetrile's Origin

Several versions of Laetrile's development have been published.

In a 1962 book, Krebs, Sr., said that he had theorized that "cancer proteins" could be broken down by an enzyme he had prepared when he was a pharmacy student. When the substance proved too toxic in animal experiments, he boiled it and obtained better results. However, according to Michael Culbert, another prominent Laetrile promoter, Krebs ran a lucrative business analyzing smuggled whiskey for wood alcohol and developed Laetrile while working on a bourbon flavoring extract. During experiments with a mold growing on the barrels in which the whiskey was aged, he isolated an enzyme that he thought might have anti-tumor activity. When his supply of barrel mold was exhausted, he switched to apricot pits and used extracts (which he called Sarcarcinase) for various tests on animals and humans during the next two decades. In 1949, Krebs, Jr., modified his father's extraction process and named the result Laetrile.

Then he dated Laetrile's birth to 1951 and said he had tested it on patients but kept no records . Noting that this version was made public much earlier than the others, Dr. Young suspects that Laetrile's origin was backdated to try to evade new drug provisions of 1938 and 1962 FDA laws. In 1977, after thorough investigation, FDA Commissioner Donald Kennedy concluded:

While it appears that Dr. Krebs, Sr., was utilizing some substance, which apparently had the trademark Sarcarcinase, before 1938, there is no evidence that the substance is identical . . . to the present-day Laetrile .

In 1945, Krebs, Jr., founded the John Beard Memorial Foundation to "develop and apply" Beard's theories. In 1950, the Krebs published a version of Beard's thesis and stated that amygdalin kills trophoblast cells where trypsin has failed. They claimed that cancer tissues are rich in an enzyme that causes amygdalin to release cyanide which destroys the cancer cells. According to this theory, noncancerous tissues are protected from this fate by another enzyme which renders the cyanide harmless. After enforcement agencies began trying to ban Laetrile as a drug, the Krebs claimed that amygdalin is a vitamin ("B17") and that cancer is caused by a deficiency of this vitamin. None of these theories is valid.

Claims for Laetrile effectiveness have also shifted. At first it was claimed to cure cancer. Later it was claimed to "control" cancer. When the "vitamin" theory was developed, it was touted as a cancer preventive. It has also been claimed to be effective in relieving pain associated with cancer and in facilitating treatment with chemotherapy.

One of the first practitioners to use Laetrile was Arthur T. Harris, M.D., who had trained in Scotland and reportedly studied embryology under John Beard. Harris, who had been doing family practice in Southern California, renamed his office the Harris Cancer Clinic. Within a year he submitted a report to Coronet Magazine which claimed that he was "working on something out here that is going to be the answer to cancer if there will ever be one," but the magazine did not report what he was doing.

By that time, the California Medical Association was receiving inquiries about Laetrile. When members of its Cancer Commission approached Krebs, Sr., he claimed that "limited" trials of toxicity in animals had been performed with satisfactory results, but that the records had been destroyed. No human trials involving Laetrile had been undertaken, but the Commission was offered case reports of patients in which spectacular results had supposedly been observed. However, the details claimed by the Krebs team could not be confirmed by other sources. The Commission was able to obtain a small supply of Laetrile for animal tests at three medical centers—all of which produced negative results.

At one point, the Krebs' agreed to supply Laetrile for a controlled clinical investigation at Los Angeles County Hospital. But later they said they would do so only if a Laetrile advocate were put in charge—which was not acceptable to hospital authorities.

The Commission then evaluated the records of 44 patients treated according to the Krebs' recommendations. Two years had elapsed since the first of these patients had been treated with Laetrile.

Nineteen had already died and there was no evidence that Laetrile had helped any of the others.

McNaughton, who has been dubbed Laetrile's "godfather" by its supporters. McNaughton is the son of the late General A.G.L. McNaughton, commander of the Canadian Armed Forces during World War II. General McNaughton also served as president of the United Nations Security Council and the National Research Council of Canada.

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When the FDA forced Hoxsey to abandon his Dallas clinic, his successor began treating cancer patients with Laetrile . The FDA made its first seizure of Laetrile at the clinic in 1960. A nurse who had long been on Hoxsey's staff carried his medications across the border to Mexico, where they are still prescribed for cancer . That is true also of Laetrile, but before its almost complete exile Laetrile provoked "one of the most politicized medical disputes in American history."

The Laetrile of commerce was amygdalin, a chemical first isolated from bitter almonds in 1830 by two French chemists, although the product Ernst Krebs, Jr., trademarked as Laetrile had a slightly different structure The significant ingredient was cyanide, some six percent by weight , and by centering on this poison Krebs fashioned his first explanation as to how Laetrile combated cancer . When the Laetrile molecule reaches the cancer site, Krebs argued, an enzyme especially abundant in cancerous areas splits the molecule, releasing hydrogen cyanide to kill the cancer.

Another enzyme protects normal cells, detoxifying any cyanide that strays into them. Thus Laetrile purportedly fulfills a prime objective of cancer chemotherapy: specificity of action. An impressed business manager for a group of doctors opined that Krebs had made a major step toward receiving a Nobel Prize. Soon, however, cancer specialists were to deny Krebs's premise. The normal cells turn out to contain more of the molecule-cleaving enzyme than do neoplastic tissues. Indeed, Laetrile administered by injection undergoes scarcely any metabolic breakdown and is excreted virtually intact in the urine. Laetrile taken orally, however, can be split by ingredients in food, releasing its poison and placing the person at grave risk. Indeed, both Laetrile and apricot kernels from which it was made killed a number of people .

Under the management of the two Krebs, father and son, Laetrile developed modest sales but encountered increasing criticism from cancer scientists and the beginning of legal restraints from both California and federal regulators. Indeed, in time, the would-be Nobelist spent several months in jail .

A series of happenstances lofted Laetrile into the national limelight. As the Krebs pair faltered, a Canadian adventurer, Andrew R. L. McNaughton, took control of Laetrile's destinies.

He trumpeted his discontent when he failed to secure an investigational New Drug exemption from the Food and Drug Administration, even though he had not submitted adequate evidence. He expanded his drum-beating, placing in the Hearst American Weekly articles penned by G. D. Kittler, the man who thought Krebs, Jr., should win a Nobel Prize. This admirer then published a paperback, promising that Laetrile would "be to cancer what insulin was to diabetes." McNaughton gained a recruit from within the cancer research establishment, Dean Burk, who gave Laetrile a semblance of scientific legitimacy. McNaughton sought to escape rising regulatory pressures by establishing manufacturing and treatment facilities in Tijuana, to which American patients began to go and from which Laetrile was smuggled into the United States and distributed clandestinely.

To McNaughton's assistance came a growing network of institutional support. The first patient treated in Tijuana established the International Association of Cancer Victims and Friends to publicize Laetrile, help cancer victims get to Mexico, and fly the flag of medical freedom. This organization and another that seceded from it, the Cancer Control Society, had unusual success in bringing Laetrile's message to members of the middle class, including some with considerable education . More important still for Laetrile's expansion of social and political influence was the arrest in 1972 of a California physician, John A. Richardson, for prescribing Laetrile in violation of the state's antiquackery law. Two trials ended with hung juries. The California Board of Medical Quality Assurance then stepped in and revoked Richardson's license on grounds of incompetence and gross negligence.

These events upset some of Richardson's fellow members of the John Birch Society. Such dedicated disciples of freedom-from-government doctrine saw in this physician's case a prime example of bureaucratic oppression. Led by Robert W. Bradford, a nuclear technician at Stanford University, Richardson's friends formed the Committee for Freedom of Choice in Cancer Therapy. By 1977 Bradford claimed five hundred chapters with some 35,000 members throughout the nation. Experienced in Birch battles against fluoridation and sex education, Committee members used a wide variety of tactics to condemn the community of cancer scientists, to castigate its allegedly futile therapeutic methods of cutting, burning, and poisoning, and to make any governmental interference with a cancer patient's right to use Laetrile or any other unorthodox treatment seem a violation of the Constitution and the fundamental rights of man.

Laetrile at this time, although still the same substance, had changed guises again. Ernst Krebs, Jr., while retaining much of his original theory as to Laetrile's mode of action, had converted cancer to a deficiency disease and transformed Laetrile from a chemotherapeutic drug to a vitamin, designated B-17. In addition to controlling cancer, B-17 could now prevent it. Nutritional scientists denied that Laetrile fulfilled any of the criteria for a true vitamin. "In short," summed up veteran vitamin researcher Thomas H. Jukes, "nothing could be less like a vitamin than laetrile." Such criticism did not deter Laetrile enthusiasts. Krebs, Jr., testifying before Senator Edward Kennedy's Subcommittee on Health in 1977, termed Laetrile "a scientific revolution as profound as the germ theory of disease ... and the Copernican theory." What Vitamin C is to scurvy, niacin to pellagra, and Vitamin D to rickets, he asserted, Vitamin B-17 is to cancer . If every American took Laetrile regularly, Dr. Richardson told the subcommittee, "in 20 years cancer would be relegated to the dusty pages of history."

Besides fighting a propaganda battle in the arena of public opinion, Laetrile's champions sought victories in legislatures and courts. The main legislative effort came in the states. Alaska passed the first law giving Laetrile special distribution status, and by the early 1980s half the states had enacted statutes, the terms varying from place to place. . Members of the Committee for Freedom of Choice played a major lobbying role in the state campaigns.

The most significant judicial encounter began with patients who had returned from Laetrile clinics in Mexico and wanted to prevent the Food and Drug Administration from interfering with their imports of the amygdalin product for continuing treatment.

At the Tijuana clinic, he had been treated with Laetrile and enzymes, and an intestinal polyp had been cauterized. Cancer specialists believed that the excision of a polyp solved the problem in a high proportion of cases, but Rutherford wanted the reassurance of Laetrile. In 1975 he won this right from a federal judge in Oklahoma. Judge Luther Bohanon ruled that Rutherford and all other cancer patients as a class who secured physicians' affidavits designating them as terminally ill could import a limited amount of Laetrile in both injectable and oral forms for their personal use.

The Circuit Court, taking into account amygdalin's hazard when ingested by mouth, barred oral dosage forms. The Supreme Court ruled unanimously that the safety and efficacy standards of the law did indeed apply to terminal patients. Despite the Court's failure to address all other issues explicitly, "the tone of the opinion," commentators observed, "left no doubt as to the Supreme Court's determination to uphold the FDA ban on laetrile." The Circuit Court so interpreted the decision and ordered judge Bohanon so to rule. He finally did so in 1987.

The FDA then issued an Import Alert, stating that, as an unapproved drug, Laetrile under its various designations could not be brought into the country .

Along this extended judicial trail, the Food and Drug Administration was ordered to conduct administrative proceedings, and Commissioner Donald Kennedy and his staff turned this task into as thorough and insightful a review of a highly promoted unorthodox drug as could be found in the American literature . The report countered the various claims made for Laetrile's effectiveness in cancer, disputing the shifting theories, remarking upon the inadequate anecdotal character of pro-Laetrile reporting, and citing the lack of promise in numerous well-controlled animal studies made at the National Cancer Institute and private cancer research centers.

The report criticized as unpersuasive the few animal tests interpreted as favorable to Laetrile by Dean Burk and others. The commissioner found that Laetrile's appeal lay in the psychology of patients and their families caught in the crushing cancer crisis. The "disparagement of conventional therapy" by Laetrile advocates was "morally reprehensible," leading sufferers away from proven treatment.

Commissioner Kennedy further met the "freedom of choice" argument head-on. Congress had decided, he noted, "that the absolute freedom to choose an ineffective drug was properly surrendered in exchange for the freedom from the danger to each person's health and well-being from the sale and use of worthless drugs." In any case, the choice to use Laetrile, made in an atmosphere of double stress, compounded from the fear of disease and the zeal of Laetrile advocates, with seldom any "rational laying out of competing arguments," could not accurately be described as free.

The litigation and the legislative battles in the states made Laetrile an issue of national concern. News magazines carried cover stories, and high-ranked television programs looked at Laetrile . Conservative columnists, most notably James J. Kilpatrick, attracted to the freedom of choice theme, gave Laetrile favorable attention . The promoters intensified their own publicity with a series of paperback books . The National Health Federation put leading Laetrile figures—including Andrew McNaughton and Glen Rutherford—on its board of governors and gave the Laetrile cause continuing support with publicity, financing, and legal aid . A majority of Americans came to believe decriminalization of Laetrile would be a good idea . Some Laetrile leaders sounded smug about their prospects .

"Rest assured, gentlemen," Bradford told Senator Kennedy's subcommittee, "that the people demand Laetrile.

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Some of the major components of the "metabolic" treatments (vitamin C, laetrile, DMSO, cellular treatment, hydrogen peroxide, and ozone) are also discussed in this chapter. The treatments are presented in alphabetical order according to the name of the main practitioner or the substance used.

DMSO is commonly used in unconventional cancer treatments, particularly in "metabolic" treatments, such as those offered at several clinics in Tijuana and in the United States (e.g., at a hospital in Zion, Illinois and at clinics in Nevada, Pennsylvania, and California (289)). DMSO is often combined with laetrile and vitamin C, among other substances, and administered to patients intravenously. For example, the "Manner Cocktail," consisting of 10cc of DMSO, 25 grams of vitamin C, and 9 grams of laetrile dissolved in a 250cc bag of a 5% dextrose solution (574), is used to treat cancer patients at the Manner Clinic in Tijuana.

Laetrile

Laetrile is perhaps the best known unconventional cancer treatment of the past two decades. In the mid-1970s, an estimated 70,000 people had used it for cancer treatment, pain control, or cancer prevention (274), and by 1979, 21 States had legalized its use (722). During the same period, laetrile had become the focus of a political and legal controversy about patients' access to unapproved drugs (see ch. 10) (396,525,578,648,705). Since the early 1980's, laetrile has lost much of its popular appeal, but is currently available at many of the unconventional cancer clinics in Mexico, used by U.S. patients.

Amygdalin, laetrile, Laetrile (capitalized), sarcarcinase, and nitriloside are some of the names of chemically related substances given to patients as laetrile treatment (903). Proponents have also referred to the treatment as a vitamin ("B-17") even though it has never been recognized as such by the scientific community. One of these names, Laetrile, is the tradename for a substance chemically related to amygdalin, a substance found naturally in pits of apricots and other fruits. In this report, the term "laetrile" is used to refer generally to this group of closely related substance(s) used in unconventional cancer treatment. Laetrile was named in reference to its biochemical properties; it was laevorotatory, or left-handed, to polarized light and belonged to the mandelonitrile class of chemicals.

Laetrile was developed from an extract of amygdalin by Ernst Krebs Sr., MD, and Ernst Krebs, Jr., and was first used to treat cancer patients in California in the early 1950's. Its use in the United States, Mexico, and Canada gradually expanded in the 1960s, as various laboratories were set up to produce and market the substance (985). The popularity of laetrile increased dramatically in the early 1970's when members of the ultraconservative John Birch Society came to the aid of a physician and fellow member who had been arrested for illegally treating patients with laetrile.

Using this case as a starting point, several Birch Society members joined together to found the "Committee for the Freedom of Choice in Cancer Therapy," primarily to advocate the right of cancer patients to use laetrile (722). Other groups, such as the Cancer Control Society and the National Health Federation, actively promoted the use and legalization of laetrile (962).

With the support of Andrew McNaughton, a Canadian businessman, several factories around the world were built to manufacture laetrile (101).

Some proponents of laetrile cite a theory of cancer etiology known as the "unitarian" or "trophoblastic" theory as the basis for treating cancer with laetrile. First proposed by John Beard in 1902 and later expanded on by Ernst Krebs, Jr., in the 1940s and 1950s, that theory draws a connection between cancer cells and trophoblast cells, which are cells present during pregnancy that are thought to protect the fertilized egg from rejection by the woman's immune system. Both cancer cells and the trophoblast cells are described in the trophoblast theory as invasive, erosive, corrosive, and capable of being carried through the bloodstream to other parts of the body. According to the theory, trophoblast cells could develop at various places in the body from precursor cells distributed throughout the body during embryonic development, and that these precursor cells could, under certain circumstances, become cancer cells. Laetrile proponents have also proposed that cancer is a deficiency disease caused by a lack of laetrile ("vitamin B-17") in the diet (362).

When laetrile is subjected to enzymatic breakdown in the body, it breaks down into three chemicals: glucose, benzaldehyde, and hydrogen cyanide (545). Various preparations of benzaldehyde have been studied recently, mainly in Japan, for antitumor activity in experimental animals (581) and in preliminary clinical studies (481,482). Cyanide has well known toxic effects on human cells, both normal and malignant (197).

Laetrile proponents claim that laetrile kills tumor cells selectively, while leaving normal cells alone. In support of this, Ernst Krebs, Jr., hypothesized that normal cells produce an enzyme, beta-glucosidase, that breaks down laetrile, releasing cyanide, which is then converted by a second enzyme, rhodanese, to the less toxic thiocyanate molecule; cancer cells, however, lack the enzyme rhodanese, according to Krebs' theory, and therefore are killed by the free cyanide (704,903).

In the 1970's, proponents claimed that laetrile had direct antitumor effects, relieved pain associated with advanced cancer, and helped to prevent cancer (903). In recent years, specific claims of antitumor activity of laetrile have rarely been made.

Instead, laetrile is more often discussed in the context of "metabolic" regimens, with claims made for antitumor responses and life extension resulting from the use of a combination of treatments, including laetrile, DMSO, vitamins, minerals, amino acids, enzymes, oxygen treatment, cellular treatment, and other substances (97,239,576).

Since laetrile itself is about 6% cyanide by weight, cyanide toxicity is possible when laetrile is broken down in the body.

If an excessive amount of laetrile is ingested, or if something is done to accelerate or increase the release of cyanide from laetrile, then toxic and lethal levels of cyanide can be reached.

B-glucosidase, the enzyme that can markedly accelerate the release of cyanide from laetrile, is found in common foods as such raw almonds, other nuts, bean and alfalfa sprouts, peaches, lettuce, celery, and mushrooms (784). When laetrile is simultaneously ingested with a source of the B-glucosidase enzyme, toxic cyanide levels may result. Cyanide toxicity has been observed in patients receiving laetrile, although many patients have taken it without showing any significant clinical signs of cyanide toxicity (620,623).

Common adverse effects noted in the studies (described later in this section) by Moertel and colleagues at the Mayo Clinic were nausea, vomiting, headache, and dizziness. Isolated reports of deaths due to cyanide poisoning following the ingestion of laetrile have appeared in the literature (100,585,644,697,768,779,800,811).

Samples of Mexican laetrile were examined at NCI for potency, content, and quality of manufacture (248,249). It was found that the measured potency of the samples differed substantially from the labeled potency. In addition, of approximately 1500 ampules that were examined visually, about 400 contained particulate matter, and 20 showed microbial growth (primarily budding yeast and fungal hyphae), indicating contamination of the material. These contaminants pose additional risks of complications, especially when given intravenously to patients who may be immunosuppressed. Bradford and colleagues at the American Biologics clinic in Tijuana have noted the existence of "pure" and "decomposed and degraded" products sold as laetrile or amygdalin (97).

Attempts at Evaluating Laetrile

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Online Laetrile Vendor Ordered to Shut Down

President of Christian Brothers Contracting Corporation based in Queens, N.Y., Vale signed a consent decree of permanent injunction on Nov. 16, 2000, agreeing to stop making and selling amygdalin products, better known as laetrile, vitamin B-17, and apricot kernels. Despite warnings from the Food and Drug Administration, Vale, who operated several Web sites out of the basement of his home, promoted and dispensed these products with false promises that they could prevent, and even cure, cancer. The consent decree, which resulted from inspections of Vale's home office and several undercover purchases, ensures that the drug supplier keeps his commitment to FDA and never sells laetrile again.

Laetrile products have been the subject of much controversy over the last 25 years. In particular, though laetrile is not the same as the chemical amygdalin-a plant compound found in the pits of many fruits, raw nuts and other plants, the two names are used interchangeably because laetrile (an acronym for laevorotatory and mandelonitrile) is a purified form of amygdalin. And mandelonitrile is a structural component of both. But while some champion the use of amygdalin and laetrile products for treating and controlling cancer, neither has ever been proven effective for this purpose, nor have they been approved by FDA for any purpose. Moreover, a National Cancer Institute-sponsored study by Charles Moertel and others, published in the January 1982 issue of The New England Journal of Medicine, concluded that laetrile is not effective as a cancer treatment and can be harmful. In fact, once it breaks down in the intestinal tract, laetrile releases hydrogen cyanide, which can result in deadly cyanide poisoning.

FDA first learned of Vale's Internet promotions through reports of unsolicited e-mails consumers received from Christian Brothers that promoted the laetrile products for cancer prevention and as a cure. Concerned about the consumer complaints, FDA investigators inspected Vale's home office in Queens, N.Y., unannounced, on Nov. 12, 1997. Vale not only watched inspectors collect samples of his laetrile products, but he also acknowledged having full responsibility for marketing them through his Internet site.

Several months later, FDA investigators went undercover and ordered from Christian Brothers a "starter package" for $248.65 that included injectable laetrile, laetrile tablets, and apricot kernels. Christian Brothers shipped the products from New York to a location in New Jersey, along with various promotional materials, including a book and video entitled "World Without Cancer." The materials were accompanied by a cover letter advising users to "Eat seeds," and telling them that "People are dying all over from a disease that can so simply be prevented." The label on the video box invited customers to visit the apricotsfromgod.com Web site.

Following the undercover purchase and results of the November 1997 sample collection, FDA sent Vale and Christian Brothers a warning letter on Oct. 28, 1998, stating that his laetrile products were unapproved new drugs and that he was breaking the law. The letter said that FDA could bring an enforcement action against Christian Brothers, which could shut the company down.

Through its lawyer, Christian Brothers responded in a Dec. 16, 1998, letter, claiming that the laetrile products were considered food for special dietary use by virtue of their ingredients.

Christian Brothers continued to sell the laetrile products.

An undercover FDA investigator telephoned Christian Brothers in January 1999 and purchased laetrile products specifically to treat melanoma. A man identifying himself as "Jason" guaranteed the investigator that laetrile products could "cure melanoma in six weeks." On Jan. 19, 1999, the investigator received a starter package from a location in Pennsylvania that contained similar items to those in the previous undercover purchase.

In February 1999, FDA conducted a follow-up inspection of Vale's home office. Inspectors found in a refrigerator eight units of 100 mg "Amigdalina B17" tablets and eleven 16-ounce bags of apricot kernels. Vale also refused to show investigators shipment records or invoices for laetrile products that the agency learned had originated in Mexico. And Christian Brothers continued to deny that its products were drugs, claiming instead that they were intended for use as "dietary supplements." Vale's attorney, however, did tell FDA that his client no longer intended to distribute laetrile in its injectable form.

But an FDA investigator, this time posing as a patient with kidney cancer, phoned Christian Brothers on May 29, 1999, asking specifically to purchase injectable laetrile. As requested by the operator, the investigator sent to the firm a money order for $238.95 and a letter stating that he wanted to order the "starter package" of laetrile products for the treatment of kidney cancer. And on June 4, the investigator received the products he had ordered, including the injectable laetrile that Vale had earlier assured FDA he was no longer selling.

After receiving the illegal drug, FDA investigators further searched the Internet and found christianbrothers.com, heavenlyhealing.com, and canceranswer.com listed as Vale's other Web sites. These sites described the nature of cancer and the failure of chemotherapy to treat it. They also contained letters and testimonials from people who had supposedly bought and used the products, and offered a list of frequently asked questions such as, "How long does it take for the cancer to die out after taking laetrile products?" Christian Brothers answered, "The cancer cells start dying immediately." As of May 28, 1999, 62,299 hits had been recorded on the christianbrothers.com site, alone.

As a result of the preliminary injunction and the subsequent consent decree of permanent injunction, Vale was ordered never again to sell laetrile products

Despite the permanent injunction, an undercover investigation by the United States Attorney's Office for the Eastern District of New York and by FDA's Office of Criminal Investigations demonstrated that Vale set up a shell corporation in Arizona through which he continued to sell Laetrile. Although he announced over the Internet that he had stopped selling Laetrile because the court had ordered him not to sell it, he continued to tout it as a cancer cure and said that other companies still sold it. If customers called Christian Brothers and tried to purchase Laetrile, Vale and his employees referred them to what they said was an unrelated company at a toll-free number. The undercover investigation demonstrated that the toll-free number rang inside Vale's own house and that outgoing packages would be sent with a "return address" that was a mailbox Vale rented in Phoenix, Arizona. Investigators also found a large supply of laetrile stored in Vale's basement ready for shipping. In March 2002, the U.S. Government asked the Court to find Vale in criminal contempt.

100. Braico, K.T., Humbert, J.R., Terplan, K.L., et al., "Laetrile Intoxication. Report of a Fatal Case," N. Engl. J. Med. 300(5):238-240, 1979.

248. Davignon, J.P., "Contaminated Laetrile: A Health Hazard," N. Engl. J. Med. 297(24):1355-56, 1977.

249. Davignon, J.P., Trissel, L.A., and Kleinman, L.M., "Pharmaceutical Assessment of Amygdalin (Laetrile) Products," Cancer Treat. Rep. 62:99-104, 1978.

274. Ellison, N.M., Byar, D.P., and Newell, G.R., "Special Report on Laetrile: The NCI Laetrile Review," N. Engl. J. Med. 299(10):549-552, 1978.

355. Gonzalez, N., "No Toxicity With Coffee Enemas or Laetrile," (letter), Townsend Letter for Doctors 64:496-497, November 1988.

381. Harris, A.T., "Terminal Cases of Malignancy Treated with Laetrile," A New Approach to the Conquest of Cancer, Rheumatic and Heart Diseases, H.H. Beard (ed.) (New York, NY: Pageant Press, 1962).

439. In re Hofbauer, 419 N.Y.2d at 940-41 as cited in G.M. Lerner, and J.E. Weeks, "The Laetrile Power Play in Drug Marketing," Hamline Law Review 3(1):1-50, 1980.

440. In re Hofbauer, 47 N.Y.2d 648, 393 N.E. 2d 1009, 419 N.Y.S.2d 936 (1979), as cited in Ohio State Law Review, "The Uncertain Application of the Right of Privacy in Personal Medical Decisions: The Laetrile Cases," Ohio State Law Journal 42(2):523-550, 1981.

525. Lerner, G.M., and Weeks, J.E., "The Laetrile Power Play in Drug Marketing," Hamline Law Review 3(1):1-50, 1980.

578. Markle, G.E., and Petersen, J.C. (eds.), Politics, Science, and Cancer: The Laetrile Phenomenon (Boulder, CO: Westview Press for the American Association for the Advancement of Science, Washington, DC, 1980).

585. Maxwell, D.M., "Increased Cyanide Values in a Laetrile User," Can. Med. Assoc. J. 119:18, 1978.

623. Moertel, C.G., Fleming, T.R., Rubin, J., et al., "A Clinical Trial of Amygdalin (Laetrile) in the Treatment of Human Cancer," N.

627. Monaco, G.P., "The Impact of the Laetrile Phenomenon on the Legal Profession: Technology by Experiment or Technology by Oath Helpers, Part II," Jurimetrics Journal of Law, Science and Technology 21(3):285-328, 1981.

643. Morrone, J.A., "Chemotherapy of Inoperable Cancer. Preliminary Report of 10 Cases Treated with Laetrile," Exp. Med. Surg. 20:299-308, 1962.

644. Morse, D.L., Boros, L., and Findley, P.A., "More on Cyanide Poisoning from Laetrile," N. Engl. J. Med. (letter), 301(16):892, 1979.

653. N.Y. Fam. Ct. Act, Section 1012(f)(i)(A), as cited in G.M. Lerner, and J.E. Weeks, "The Laetrile Power Play in Drug Marketing," Hamline Law Review 3(1):1-50, 1980.

662. Navarro, M.D., "Laetrile Therapy in Cancer," Philippine J. Cancer 4: 204-209, 1962.

692. Ohio State Law Journal, "The Uncertain Application of the Right of Privacy in Personal Medical Decisions: The Laetrile Cases," Ohio State Law Journal 42(2):523-550, 1981.

697. Ortega, J.A., and Creek, J.E., "Acute Cyanide Poisoning Following Administration of Laetrile Enemas," J. Pediatr. 93:1059, 1978.

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Walter Douglas Brodie, M.D., was convicted twice of failing to file income tax returns. In 1977, he was sentenced to six months in prison, and in 1987 he was fined $10,000 and sentenced to one year in prison and five years' probation. In a 1983 letter describing how he has prescribed laetrile and other "alternative" cancer treatments, Brodie stated that he had moved his practice to Nevada after "political persecution" by the California State Board of Medical Quality Assurance, which had unsuccessfully attempted to discipline him several times.

Although he maintained that ADS was a "nutritional supplement," analysis showed it to be 99.4 percent water and a brownish sludge composed mainly of coliform bacteria (the same bacteria found in human feces). Halstead, who operated the Halstead Preventive Medicine Clinic in Colton, California, has been a leading promoter of laetrile, chelation therapy, and many other questionable practices.

was a central figure in the worldwide promotion of laetrile. In 1977, he was placed on two years' probation after pleading guilty to a criminal charge of conspiracy to facilitate the transportation of smuggled laetrile. He had a prior conviction in Canada for a stock fraud.

James R. Privitera, Jr., M.D., was convicted in 1975 and sentenced to six months in prison for conspiring to prescribe and distribute laetrile. In 1980, after the appeals process ended, he served fifty-five days in jail.

Then, because he had been prescribing unapproved substances (including laetrile, calcium pangamate, and DMSO) for the treatment of cancer, the California Board of Medical Quality Assurance suspended Privitera's medical license for four months and placed him on ten years' probation under board supervision. During the probationary period, Privitera was "prohibited from making any representation that he is able to cure cancer through nutrition." He was also forbidden to tell a patient he had cancer unless the diagnosis had been confirmed in writing by an appropriate board-certified specialist.

Frank Salaman, a current board member and former husband of NHF president Maureen Salaman, was convicted in 1977 of conspiring to smuggle laetrile.

Emory Thurston, who died in 1981, was an active promoter of laetrile and displayed pamphlets he had edited at a booth at NHF conventions. At a 1973 convention, when approached by an agent of the California Bureau of Food and Drug who said she had cancer of the uterus, Thurston offered to supply her with laetrile. He instructed the agent to contact him at his office at the Institute for Nutritional Research in Hollywood. He later sold laetrile to the agent and advised her not to have surgery. After additional evidence was gathered, Thurston was convicted, fined, and placed on probation for two years.

The Promotion of Laetrile

Because laetrile lacks FDA approval, it is illegal to market it in interstate commerce. In 1977, a federal court set up an "affidavit" system under which personal supplies of laetrile could be imported into the United States by cancer patients certified by a physician as "terminal." The plaintiff in the case was Glen Rutherford, a Kansas seed salesman who believed that laetrile was needed to keep him alive. Although the U.S.

From 1978 to 1982, NHF published Public Scrutiny, a monthly newspaper (later converted to a magazine) whose primary focus was on laetrile and "metabolic therapy." Most of its original staff members were prominent promoters of laetrile, and three of its advisers had been convicted of laetrile-related crimes. Each issue of Public Scrutiny contained a full-page ad from the Laetrile Information Center, a company near the Mexican border that would arrange for legal importation. Mexican clinics and other sellers of laetrile also advertised regularly in Public Scrutiny.

After NHF governor James Privitera, M.D., was charged with a laetrile-related offense, appeals in Public Scrutiny

Chad attracted nationwide attention when his family moved to Mexico to defy a Massachusetts court order that the boy receive proper therapy and stop getting laetrile. The October 1979 issue of Public Scrutiny described how Chad was thriving, how his father was studying for a career as a "nutrition consultant," and how Chad's mother had stopped his chemotherapy without telling the Mexican clinic doctor. A few days after the newspaper was distributed, Chad died. His parents continued to promote laetrile and to claim that Chad died because he had "lost the will to live." However, the autopsy showed recurrent leukemia, and cyanide (a breakdown product of laetrile) in his liver and spleen.

NHF also assisted the parents of Joey Hofbauer, an eight-year-old boy with Hodgkin's disease, a form of cancer usually curable in its early stages. In 1977, New York State authorities sought custody of Joey because his parents chose laetrile over effective treatment for the boy. With NHF attorney Kirkpatrick Dilling representing the parents, the court ruled that they were "concerned and loving" and "not neglectful" in rejecting conventional treatment. After eighteen months of laetrile and megavitamin treatment from Michael Schachter, M.D. (a New York psychiatrist who occasionally lectures at NHF conventions), Joey was moved to the Bahamas for another type of questionable treatment. He died in 1980 with lungs full of tumors.

A bill to exempt laetrile from FDA jurisdiction was introduced by Public Scrutiny's legislative advisor, physician-Congressman Larry McDonald (D-GA). In 1979, a malpractice suit against him by survivors of a patient he had treated with laetrile was settled for $30,000. NHF's efforts to exempt laetrile petered out after McDonald was killed in the crash of the Korean airliner shot down by the Soviets in 1983.

He was joined in this effort by Dean Burk, a retired National Cancer Institute employee who was also a leading promoter of laetrile.

Gerson therapy is still actively promoted by his daughter, Charlotte Gerson, through lectures, talk show appearances, and publications of the Gerson Institute in Bonita, California. Gerson protocols have included liver extract injections, ozone enemas, "live cell therapy," thyroid tablets, royal jelly capsules, linseed oil, castor oil enemas, clay packs, laetrile, and vaccines made from influenza virus and killed Staphylococcus aureus bacteria.

Laetrile

Laetrile, which achieved great notoriety during the 1970s and early 1980s, is the trade name for a synthetic relative of amygdalin, a chemical in the kernels of apricot pits, apple seeds, bitter almonds, and some other stone fruits and nuts. Many laetrile promoters have called it "vitamin B17" and falsely claimed that cancer is a vitamin deficiency disease that laetrile can cure.

Claims for laetrile's efficacy have varied considerably .

First it was claimed to prevent and cure cancer. Then it was claimed not to cure, but to "control" cancer while giving patients an increased feeling of well being. More recently, laetrile has been claimed to be effective, not by itself, but as one component of "metabolic therapy" (described below).

Laetrile was first used to treat cancer patients in California in the 1950s. According to proponents, it kills tumor cells selectively while leaving normal cells alone. Although laetrile has been promoted as safe and effective, clinical evidence indicates that it is neither . When subjected to enzymatic breakdown in the body, it forms glucose, benzaldehyde, and hydrogen cyanide . Some cancer patients treated with laetrile have suffered nausea, vomiting, headache and dizziness, and a few have died from cyanide poisoning.

Laetrile has been tested in at least 20 animal tumor models and found to have no benefit either alone or together with other substances.

In response to political pressure, a clinical trial was begun in 1982 by the Mayo Clinic and three other U.S. cancer centers under NCI sponsorship. Laetrile and "metabolic therapy" were administered as recommended by their promoters. The patients had advanced cancer for which no proven treatment was known. Of 178 patients, not one was cured or stabilized, and none had any lessening of any cancer-related symptoms. The median survival rate was about five months from the start of therapy. In those still alive after seven months, tumor size had increased. Several patients experienced symptoms of cyanide toxicity or had blood levels of cyanide approaching the lethal range .

In 1975, a class action suit was filed to stop the FDA from interfering with the sale and distribution of laetrile. Early in the case, a federal district court judge in Oklahoma issued orders allowing cancer patients to import a six-month supply of laetrile for personal use if they could obtain a physician's affidavit that they were "terminal." In 1979, the U.S. Supreme Court ruled that it is not possible to be certain who is terminal and that even if it were possible, both terminally ill patients and the general public deserve protection from fraudulent cures.

In 1987, after further appeals were denied, the district judge (a strong proponent of laetrile) finally yielded to the higher courts and terminated the affidavit system . Few sources of laetrile are now available within the United States, but it still is utilized at several Mexican clinics.

Proponents of "metabolic therapy" claim to diagnose abnormalities at the cellular level and correct them by normalizing the patient's metabolism. They regard cancer, arthritis, multiple sclerosis, and other "degenerative" diseases as the result of metabolic imbalance caused by a buildup of "toxic substances" in the body. They claim that scientific practitioners merely treat the symptoms of the disease while they treat the cause by removing "toxins" and strengthening the immune system so the body can heal itself. The "toxins" are neither defined nor objectively measurable. "Metabolic" treatment regimens vary from practitioner to practitioner and may include a "natural food" diet, coffee enemas, vitamins, minerals, glandulars, enzymes, laetrile, and various other nostrums that are not legally marketable in the United States. No scientific study has ever shown that "metabolic therapy" or any of its components is effective against cancer or any other serious disease.

The most visible proponent of "metabolic therapy" was Harold Manner, Ph.D., a biology professor who announced in 1977 that he had cured cancer in mice with injections of laetrile, enzymes, and vitamin A. (Actually, he digested the tumors by injecting them with digestive enzymes, which cannot cure cancers that have metastasized.) During the early 1980s, Manner left his teaching position and became affiliated with a clinic in Tijuana, Mexico.

Wilson B: The rise and fall of laetrile. Nutrition Forum 5:33-40, 1988.

American Cancer Society. Unproven methods of cancer management: Laetrile. CA—A Cancer Journal for Clinicians 41:187-192, 1991.

Moertel C and others. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. New England Journal of Medicine 306:201-206, 1982

The CFCCT's formation was triggered by the arrest of John A. Richardson, MD, an Albany, California, physician who frequently prescribed laetrile. As described by a Committee official:

4. All currently used Western therapies—surgery, drugs, radiation—admittedly are dangerous and harmful to the patients in varying degrees. Therefore, the Committee does not support the FDA's ruling against the use of Laetrile (a nontoxic vitamin food supplement) on the grounds that it might be harmful.

During the 1970s, the Committee held seminars, symposia and "doctors' workshops" and distributed books, pamphlets, cassette tapes, and other information on unproven methods of cancer management. The organization also generated letter-writing campaigns in support of these methods and the practitioners who used them. The primary political goal appeared to be the passage of state and federal laws to legalize the use of laetrile.

CFCM president Robert Bradford, was also president of the Robert Bradford Research Institute (BRI), the Robert W. Bradford Foundation, American Biologics, and American Biologics Integrative Medical Center. According to a Stanford University official, Bradford graduated from San Jose State University and worked from 1963 to 1976 as an electronics engineer for the Stanford University Linear Accelerator Center . Bradford's publications include Now That You Have Cancer (a laetrile metabolic program orientation handbook); The Biochemical Basis of Live Cell Therapy, Oxidology: The Study of Reactive Oxygen Toxic Species (ROTS) and Their Metabolism in Health and Disease; and International Protocols in Cancer Management. Bradford is said to have received two honorary degrees: a "cultural doctorate in nutritional science" in 1983 from the World University and a "doctor of biochemistry degree" in 1984 from Medicina Alternativa, an "international holistic medical group" in Sri Lanka. Although these degrees have no academic standing, he generally identifies himself as "Dr. Bradford.""Robert Bradford, DSc," or Robert Bradford, "DSc, NMD." I do not know the origin of the "NMD," but it could not have come from an accredited school.

Robert Bradford's wife Carole Bradford, the Committee's secretary/treasurer, was also chief executive officer of American Biologics Integrative Medical Center and Director of the Bradford Research Institute, She is coauthor of Cookbook for Healthful Living, a book said to include recipes accompanying the American Biologics Hospital treatment program. In 1998, she announced that she had undergone successful treatment of a breast cancer at the Hospital. According to her story, a breast cyst she had removed in 1993 turned out to be an ductal cell carcinoma the size of a golf ball. She took tamoxifen (a standard drug) for two months plus 30 types of supplement, herb, and homeopathic pills and daily injections of laetrile and many other substances for several months. Later she reduced the number of pills and "crammed 12,000-gauss magnets into her brassiere as a daily kind of localized magnetic therapy." . In a 1999 interview, she stated that she considered herself "privileged because I had the best doctor—my husband—and my hospital." She also said that she was using a preventive program that dietary measures, "organic foods," nutritional supplements and colonic irrigation . Although she would like to believe that her unconventional treatments have cured her. However, ductal cancer treated with lumpectomy (lump removal) alone has a fairly good prognosis. According to one study, for example, the odds of surviving eight years without evidence of recurrence were about 60% .

Michael L. Culbert (1937-2004), a former newspaperman and freelance writer, edited The Choice for more than 20 years and served as CFCM board chairman and as vice president and public relations director of American Biologics Hospital. His books include Vitamin B17—Forbidden Weapon Against Cancer (1974); Freedom from Cancer—The Amazing Story of Laetrile (1976); Medical Revolution in America (1981); What the Medical Establishment Won't Tell You that Could Save Your Life (1984); AIDS: Terror, Truth and Triumph; AIDS: Hope, Hoax and Hoopla (1989); and Medical Armageddon (1994 and 1995). He also co-authored How You Can Beat the Killer Diseases (1977) and the books listed above by Robert Bradford. Culbert had a bachelor of arts degree from the University of Wichita and an "honorary DSc degree" from Medicina Alternativa. In 1996, Culbert founded and became president of the International Council for Health Freedom (ICHF), which was described on its Web site as "an informational clearinghouse between groups and people in all countries which pursue the objective of medical free choice and new ideas in medicine and healing." The ICHF Web site disappeared about a year after Culbert's death, and the organization appears to be defunct.

Bruce Halstead, MD (1920-2002), who for many years was the Committee's vice-president, operated the Halstead Preventive Medicine Clinic in Colton, California, and was a leading promoter of laetrile, chelation therapy, and many other questionable practices. In 1985, he was convicted of 12 counts of cancer fraud and grand theft for selling an herbal tea called ADS to ten patients with cancer and other serious diseases for $125 to $150 a quart. Although he maintained that ADS was a "nutritional supplement," analysis showed it to be 99.4% water mixed with a brownish sludge composed mainly of coliform bacteria, the bacteria found in human feces. Following the trial, which lasted five months, Los Angeles County Deputy District Attorney Hyatt Seligman called Dr. Halstead "a crook selling swamp water." He was fined $10,000 and sentenced to four years in prison, but practiced for several more years while appealing his conviction. After his final appeal was denied (1991), he was sentenced to prison and his medical license was revoked (1992) . However, the authorities apparently overlooked him and he was not incarcerated until 1997, when he served few months in prison.

American Biologics-Mexico, which opened in 1978, was described in its brochures as "North America's most advanced holistic medical center." It claimed to offer "new hope for sufferers of cancer, heart disease, MS, allergies, all forms of metabolic dysfunction." By the late 1980s, it claimed to have treated more than 15,000 patients. Ads have appeared regularly in chiropractic and health-food-industry publications. In 1988, about 75% of the hospital's patients were said to be treated for cancer . During the 1980s, I observed itemized statements to insurance companies that identified treatments as "chemother/inj" without indicating that laetrile was included .

In 1999, American Biologics stopped licensing its name to the Mexican facility (which was renamed International Biologics Hospital and Medical Center) and began operating a new Tijuana facility called American Biologics Integrative Medicine Center. The treatments listed on the center's Web site included: acupuncture; advanced oxidative therapy; anti-microbial therapy; applied kinesiology; bioelectrical therapy; bioelectrical therapy; chondroitin sulfates; colonic irrigation and/or rectal implants to establish; comprehensive antioxidant therapies; detoxification/modalities; dietary modification; DMSO (dimethyl sulfoxide); EDTA chelation treatments; enzyme therapy; genetic repair therapy; genetic therapy ("to repair or normalize the DNA of cancer cells"); hormonal and glandular supplementation; hydrotherapy; intravenous infusion therapy; laetrile therapy; live cell therapy; liver, bladder and kidney flushes; massage therapy; nutritional medicine; pulsed magnetic therapy; and oral/intravenous administration of vitamins, minerals, enzymes, amino acids, and essential fatty acids. Some standard treatment modalities are also offered. At about the same time, Culbert terminated his association with Bradford and the Choice published a few issues and then became defunct. Today, Bradford is listed as "scientific advisor" of Ingles Hospital & Integrative Medical Center in Tijuana.

American Biologics, a "metabolic pharmaceutical firm," markets products and was also the U.S. representative office for American Biologics-Mexico. During the early 1980s, the company's "professional catalog" listed enzymes, digestive aids, emulsified vitamins, minerals, Gerovital, injectable glandulars, oral glandulars, and specialty products, such as DMSO, benzaldehyde, apricot kernels, EDTA, and laetrile, as well as books, tapes and films, and lab test apparatus. In 1982, an article in The Choice stated that American Biologics was "the major amygdalin distributor in the world." In 1988, the company donated about $20,000 in money and laboratory equipment to John Bastyr College, a naturopathy school in Seattle . Its recent offerings have included shark cartilage, homeopathic products, and others that in vogue today.

In 1977, Robert Bradford, Frank Salaman (then CFCCT vice-president), Dr. John Richardson and Richardson's office manager Ralph Bowman were convicted of conspiring to smuggle laetrile. Bradford was fined $40,000, Richardson $20,000, and Salaman and Bowman $10,000 each . In 1986, a U.S. Court of Appeals upheld a tax court assessment of more than $2 million in income taxes and penalties against Bradford for income derived from smuggling laetrile from Mexico into the United States. During the proceedings, the courts concluded that Bradford (a) engaged in illegal activities, (b) failed to file federal tax returns for four consecutive years, (c) failed to report substantial business income, his salary from Stanford, and the gain on the sale of his residence, all of which he knew constituted taxable income, (d) dealt in cash to avoid scrutiny of his finances, (e) filed false W-4's, (f) made efforts to conceal his laetrile distribution activities, (g) failed to make estimated tax payments; (h) failed to cooperate with the revenue agent during the audit examination; and (i) failed to maintain adequate records .

In 1980, a few days after the Mayo Clinic began its clinical trial of laetrile the CFCCT sought a temporary restraining order. The suit charged that the amygdalin used for the test was "degraded" and would yield negative results that "would likely terminate both future testing and future use" of laetrile , the court ruled that the plaintiffs lacked standing to sue .

In 1984, the CFCM sued to intervene in Rutherford vs. United States, an action intended to stop the FDA from interfering with the sale of laetrile. The suit also sought to block interference with manufacturers, sellers, and distributors of supplies to unorthodox physicians, to cancer patients, and to others suffering from "chronic degenerative disease." Two months later, after Rutherford's attorneys and principal backers objected, CFCM's suit was withdrawn . Rutherford eventually lost the suit.

Richardson J: Laetrile Case Histories. New York City: Bantam Books, 1977, p 88.

Wilson B: The rise and fall of laetrile. Nutrition Forum 5:33-40, 1988.

Moertel C and others. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. New England Journal of Medicine 306:201-206, 1982.

Originally, Glen Rutherford, on behalf of a class of cancer patients, brought suit in Federal district court to stop FDA from prohibiting interstate shipment of laetrile. The court found the drug to be nontoxic and effective if given in the correct dosage, and permitted its limited purchase. The government appealed the decision. The U.S. Court of Appeals for the 10th Circuit upheld the lower court's injunction but directed the district court to remand the case to the Food and Drug Administration (FDA) for determination of whether laetrile was a "new drug" (within the meaning of the FDCA) and, if so, whether it was exempted from the safety and effectiveness requirements by falling under either of two grandfather clauses. FDA's determination that laetrile was a new drug that did not fall under either grandfather clause brought the case back to the district court. The presiding judge concluded that FDA's determination was incorrect (he determined that the drug was grandfathered), and that by denying cancer patients access to laetrile, FDA was infringing on the constitutionally protected right of privacy. Again the decision was appealed. However, in its decision, the court of appeals did not address the lower court's ruling, but introduced a new issue: the court found that FDCA's standards for safety and efficacy had "no reasonable application" to terminally ill cancer patients and allowed terminally ill individuals to receive laetrile. FDA appealed the decision to the U.S.

Two court cases concerning the use of laetrile have addressed the issue of parents' rights to choose an unapproved treatment for their child, both of whom had cancers that, in all probability, were curable with appropriate mainstream treatment. In both cases, the State requested that courts declare the children wards of the State, arguing that the parents' actions constituted parental neglect. However, the circumstances surrounding the parents' decisions led the courts to different opinions (525,692). In Massachusetts, Chad Green, a 2-year-old boy with acute lymphocytic leukemia, was declared a ward of the State when his parents stopped his chemotherapy while he was in remission and put him on what they called a metabolic therapy (laetrile and a nutritional regimen). Though his parents had already left the State with Chad, the State Supreme Court upheld a court order requiring he receive State-supervised chemotherapy and cease taking the unapproved treatment. The court acknowledged that parents have natural rights that encompass a private family life, but viewed the child's well-being as an overriding interest. The court based its decision of what was in the child's best interest on strong medical evidence that the unconventional treatment was not improving the child's condition, while, until the parents stopped treatments, conventional treatment had controlled the leukemia. It found the nutritional therapy "useless and dangerous" (692). Chad Green died in Mexico shortly after his parents took him there for unconventional treatment (627).

A similar case in New York, In re Hofbauer, involved a seven-year-old boy, Joey Hofbauer, with Hodgkins disease. Again the State tried to prevent the parents from continuing to treat the child with metabolic therapy (including laetrile) by pursuing a child neglect case. However, in this case the New York Court of Appeals found that the parents, who had found a licensed physician to prescribe laetrile, had not "failed to exercise a minimum degree of care" (653) since they were following a recommended treatment that had "not been totally rejected by responsible medical authority" (439). In addition, the court found some evidence that the unconventional treatment might be effective, while there was also evidence that conventional treatment was failing (440). Joey Hofbauer died a few years later, in 1980.

FDA regulations apply only to specific substances used in treatments, not to treatment regimens or practices. Among unconventional cancer treatments, the FDA regulations apply to pharmacologic agents (such as laetrile or Burzynski's Antineoplastons), biologic agents (such as vaccines or the biologic products used in Immuno-Augmentative Therapy (IAT)), herbal preparations (such as the Essiac or Hoxsey tonics), and homeopathic preparations. Under the terms of the FDCA, drugs are defined as "articles," including chemical or biological substances, "(other than food) intended to affect the structure or any function of the body of man" and "intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man" (21 U.S.C. 321(g)(1)). FDA uses product labels, promotional materials, advertisements, and oral representations to determine whether a substance is intended to be used therapeutically. Most other types of unconventional cancer treatment (e.g., psychological and metaphysical approaches, nutritional regimens) would not be considered drugs and therefore would not be subject to regulation under the FDCA as long as drug-type claims are not made for them.

The most intensive legal challenge to any provision of the FDCA was the Rutherford Case (discussed above). When Rutherford originally brought the case to court requesting the injunction to prevent the FDA from prohibiting distribution of laetrile, he challenged the legality of FDA's actions. Later, after FDA determined that the drug fell under the FDCA requirements for new drugs and was not eligible to exempted under a grandfather clause which would have exempted it from efficacy requirements, the district court found that FDA's interpretation infringed on a constitutionally protected right of privacy. When the case reached the U.S. Court of Appeals, that court did not address the statutory and constitutional issues on which the lower court ruled (that the drug was entitled to an exemption and that the law violated a constitutional right to privacy). The court of appeals did find, however, that the Act's standards of safety and effectiveness have no reasonable application to the terminally ill. This issue was also taken up by the U.S.

The Federal smuggling statute (18 U.S.C. 545) prohibits unlawful introduction of products into the United States. Possession of such products alone is sufficient for conviction under this statute; in addition, any such products are confiscated by the Government. Penalties for violating this statute include fines, imprisonment for up to five years, or both. In one case, U.S. v. Richardson, John Richardson, M.D., and three co-defendants (Ralph Bowman, his office manager, and Robert Bradford and Frank Salaman, two members of the Committee for Freedom of Choice in Cancer Therapy) were convicted of several crimes including conspiracy to smuggle laetrile from a clinic in Mexico into the United States (962). The defendants argued that FDA's classification of the drug, which prohibited its being brought into the country, was an act of governmental misconduct; they claimed their actions were justified because laetrile was unavailable but necessary in the United States. Their conviction was upheld on appeal (917). Bradford was fined $40,000, Richardson $20,000, and Salaman and Bowman $10,000 each (962).

For example, the defendants in U.S. v. Richardson were charged and convicted of conspiring to possess and distribute laetrile, and the defendants in U.S. v. Durovic (the Ivy case, see previous discussion) were charged with, but not convicted of, conspiracy (915,917).

The oldest and most comprehensive State cancer statute is California's (149). This statute established criteria for cancer treatments similar to those of the FDCA and provided a mechanism for informing the public about treatments that are considered to be unsafe or ineffective. This law also incorporated regulations making it illegal to use certain unconventional cancer treatments, including laetrile and the Hoxsey tonic, within the State.

Under this statute, James Privitera, a medical doctor, and 4 co-defendants were convicted by a jury of conspiracy to sell and prescribe an unapproved drug, laetrile, for the alleviation or cure of cancer, a felony, (described above). The law authorizes the State health agency to issue cease-and- desist orders to those who violate the State cancer law (see, e.g. chapter 5, discussion of the case of Virginia C. Livingston, M.D.). Failure to comply with these orders can lead to injunctions against the promotion of the treatments and to criminal penalties against the promoters.

One State offered the following rationale for its provision legalizing the use of laetrile in cancer treatment:

At present, at least 19 States have laws legalizing the prescription and intrastate sale of laetrile to cancer patients (two other States had this provision but repealed it). Several States enacted (and later repealed) provisions legalizing the use of IAT. Many of these laws require certain types of informed consent or limit the use of the substance to physicians.

Some of the statutes prohibit State licensing boards from disciplining physicians who prescribe laetrile. Other laws protect manufacturers from penalties associated with the manufacture or distribution of the substance.

Laws and regulations designed to protect patients from potentially harmful and ineffective treatments have been criticized by supporters of unconventional treatment for limiting patients' access to treatments of their choice. When State laws have been passed permitting access to specific unconventional cancer treatments that would otherwise be illegal (e.g., laetrile, in the 1970s), they have been criticized by segments of the mainstream medical community for exposing patients to hazardous or ineffective treatments, or for dissuading patients from seeking potential curative treatment.

Several of the unconventional treatments discussed in other sections of this report also include a spiritual or religious component. In macrobiotics, for instance, the dietary guidelines are one aspect of a much larger philosophical and spiritual system. Similarly, Anthroposophic medicine, which includes the use of the herbal preparation Iscador for cancer patients, is based on a complex religious philosophy and "spiritual science" developed by Rudolph Steiner in the late 19th and early 20th centuries. Other unconventional treatments that were designed specifically for cancer patients include a spiritual component. Spiritual aspects of the original Kelley regimen, for example, reflected the developer's strong religious beliefs. A physician who founded the first clinic in Tijuana offering laetrile to cancer patients, Ernesto Contreras, includes a strong spiritual orientation in his regimen and often leads services for patients at a chapel he built at his clinic.

Chapter 5 also describes a number of other pharmacologic and biologic agents that are used as unconventional cancer treatments, some singly and some in combination. Examples include laetrile, a substance widely popular in the 1970's and currently offered in several clinics in Mexico; vitamin C, whose most prominent advocate for use in cancer treatment is the biochemist Linus Pauling, Ph.D.; dimethylsulfoxide (DMSO), an industrial solvent often used in combination with laetrile and vitamin C; cellular treatment, processed tissue obtained from animal embryos or fetuses given orally or by injection; and various substances containing oxygen, including hydrogen peroxide and ozone taken orally, rectally, or via blood infusion. Hydrazine sulfate, a substance that, from 1975 to 1982, was on the American Cancer Society's Unproven Methods List, was taken off when clinical trials under an investigational new drug exemption (IND) were started. The trials were controversial, however, and it is still considered in the context of unconventional cancer treatments.

Some cases have come to light when parents have made that decision for a minor child and legal proceedings against the parents have ensued. A highly publicized case in the late 1970's of this type involved a child with potentially curable leukemia, whose parents decided to forgo chemotherapy for laetrile (see chapter 10 for a discussion of this case). Some unconventional practitioners have been charged criminally with discouraging people, who later died of progressive cancer, from seeking possibly curative treatment, or for failing to encourage them to seek such treatment (see ch. 11).

Insurance coverage under the Federal Medicare program (for people 65 and over) is limited to care that is "reasonable and necessary," which for drugs generally refers to those that are FDA approved, and in some cases to drugs designated by NCI as "Group C" (Group C drugs have been found to have some therapeutic value in clinical trials, but have not yet been approved by FDA). Most Blue Cross/Blue Shield and private insurance plans have similar restrictions. Most health insurance contracts contain general language that excludes coverage of unconventional treatments, and some specify particular treatments by name. Examples in some plans are exclusions of coverage for laetrile, IAT, and cell therapy. Nevertheless, a number of clinics offering unconventional cancer treatments state or imply in their brochures that the treatments costs are covered under various insurance plans, perhaps creating an expectation that patients may be reimbursed.

Formal attempts at evaluating unconventional cancer treatments have been made by the Federal Government in various ways. The best known are clinical trials of laetrile and vitamin C that were carried out by researchers at the Mayo Clinic under contract to NCI. In both instances, the Government was responding to the expanding popularity of these compounds with the public.

In the case of laetrile, although it was not approved by FDA, by 1982 its use had been legalized by more than half the States and it could be used legally in the rest of the country as a result of a court order. The published laboratory studies of laetrile's activity did not suggest that it would be active against cancer, however, and no adequate study of cancer patients had been done. Interest in the use of vitamin C, a widely available product, grew as a result of studies of cancer patients reported by Ewan Cameron in the early 1970s, later in collaboration with Linus Pauling, and because of evidence from in vitro and animal studies suggesting beneficial effects of vitamin C. The laetrile experience is discussed here.

During its period of greatest popularity, laetrile was promoted mainly as an agent that acts directly against tumor cells, and it was treated as such when the Government decided to evaluate it. The first step taken was to look for evidence that laetrile caused tumors to regress. To do this, about 450,000 physicians and other health professionals were solicited for reports of patients with documented antitumor responses to laetrile. In the end, 67 cases had sufficient information to be evaluated independently.

NCI decided to proceed with a prospective study of laetrile, carried out by researchers at the Mayo Clinic. They began with a typical "phase I" study to determine toxicity and dose (620). Those results were used in designing the phase II study of antitumor activity in 178 patients with a variety of cancer types (623). Among the 175 patients evaluable at the end of the study, one had a partial remission. No further clinical trials were deemed necessary, as the drug was considered ineffective.

A host of criticisms was heard from laetrile proponents. In the confrontational atmosphere that exists around unconventional cancer treatments, it appears impossible to resolve these questions conclusively, but this study appears to have been a fair test of the main claim for laetrile, that it was an antitumor agent.

OTA's experience during this assessment in developing a clinical trial protocol for IAT illuminated some key points. One of the most significant is that, except in rare cases, evaluation should be initiated by and the responsibility of the practitioners using or otherwise positively interested in the treatment, though they need not be (and preferably are not) associated exclusively with the treatment. (The Federal Government has initiated evaluations only when treatments have become very popular and potentially affected large numbers of patients.) Whoever undertakes these studies, it is important to involve developers or other key practitioners of the treatment in developing a plan for the study, and in reporting and publishing its results. To ensure credibility and the availability of technical expertise, the trial should, if possible, be carried out in an accredited medical institution in the United States, with the consent of the appropriate Institutional Review Boards. Finally, it is of the greatest importance that in any study the safety of patients is ensured. This may be best accomplished by carrying out studies in accordance with FDA regulations governing new and unapproved drugs and devices (when applicable).

The responsibility for best case reviews would rest with the practitioners offering unconventional treatments, ideally with technical advice from appropriate experts. This approach, still untested, would place the burden of initiating the evaluation process on the practitioner. No matter how well done, however, a best case review cannot take the place of prospective clinical trials, and no firm statements about effectiveness could be made on the basis of a best case review. It is possible that, like the review of laetrile cases, (see footnote 7) relatively little will be learned from best case reviews, despite significant effort. This will depend, to some extent, on the availability of sufficiently detailed medical records, from both unconventional and mainstream treatment. The latter, particularly, may not be accessible to unconventional practitioners.

If an unconventional treatment appears "promising" (e.g., on the basis of a best case review), there might be sufficient impetus for pursuing formal evaluation. There may, in addition, be other reasons for conducting an evaluation of an unconventional treatment. Such studies could be very important in terms of public health, though they might well not lead to advances in cancer treatment. A treatment's popularity might influence the decision. It might be considered important, for public health reasons, to evaluate treatments used by large numbers of people, e.g., treatments offered by the long-established clinics or particular treatments that gain widespread acceptance without proper clinical trials (e.g., laetrile). This is not to suggest that negative evidence will always dissuade cancer patients or that mere popularity should be taken as a sign of effectiveness. Indeed, it is clear from past experience in both conventional and unconventional medicine that the two are not necessarily synonymous. Another factor that, in the real world, might stimulate consideration of an evaluation is political interest. This was the case in OTA's undertaking protocol development for a clinical trial of IAT.

7. The laetrile review, however, was different from what is proposed here in that the Government conducted it.

AOL Wins Suit against Laetrile Spammer

2. Operating from Internet domains such as "laetrile.net" and "apricotsfromgod.com," Defendants have bombarded AOL and its members with millions of unsolicited Internet e-mail messages that advertise a purported "cancer cure" \ specifically, the consumption of laetrille (apricot seeds) sold by Defendants. Despite demands by AOL that they cease sending this junk e-mail, Defendants have refused to stop their mass mailings and have persisted in using deceptive techniques designed to frustrate AOL's ability to detect and filter this e-mail "spam." Among other things, Defendants have created a fraudulent address with the designation "aol.com" within their e-mail messages so that the messages falsely appear to originate from AOL members. Defendants' mass e-mailing of "spam" has resulted in thousands of member complaints, members terminating their AOL service and has clogged AOL's computer systems, co-opting valuable computer staff resources needed to deliver legitimate internet e-mails.

10. Upon information and belief, Defendants operate and transact business, or have operated and transacted business, from numerous InterNIC-registered Internet domains, including the following: "laetrile.net"; "amygdalin.net"; "heavenlyhealing.com"; "christianbrothers.com"; "apricotsfromgod.com"; "canceranswer.com"; "naturalhealings.com"; and "juicenoni.net".

31. Many of Defendants' promotional e-mails tout medical literature concerning a laetrile "cure" for cancer, and offer to sell laetrile itself. Copies of two such messages are attached hereto as Exhibits A and B, respectively. The e-mails often state, "If you would like to be brought to the most informative Web site on the Internet concerning cancer and the simple known answer, click on the following blue link." The e-mail then states "Click here and you'll automatically be brought to the Web site (See Exhibit A)

35. Defendants' promotional messages regarding their "cancer cures" typically direct recipients to a Web site where additional information regarding the product is located. Through that Web site the user is able to purchase, among other things, laetrile, a videotape and a book promoting Defendants' advice regarding cancer treatment. A copy of the text contained on Web site is annexed hereto as Exhibit E.

Laetrile Spammers

Also marketed as laetrile

In October 1998, the FDA warned Vale that his apricot-seed products were "new drugs" and misbranded, and that he could be subject to enforcement action if he persisted in marketing them . However, Vale's Web sites continued to make unsubstantiated claims and even hosted a copy of the FDA warning letter. In April 2000, the Justice Department obtained a preliminary injunction prohibiting Vale and Christian Brothers from making or distributing amygdalin, Laetrile, "Vitamin B-17," or apricot seeds.

Wilson B: The rise and fall of laetrile. Nutrition Forum 5:33-40, 1988.

Christian Brothers contracting corporation signs consent decree with FDA; agrees to stop selling all amygdalin/laetrile products. FDA Talk Paper T00-62, Nov 17, 2000.

Lewis, C. Online Laetrile vendor ordered to shut down. FDA Consumer 35(2):7-38, 2001.

Former Laetrile Peddler Disciplined Again

James R. Privitera, Jr., M.D., who served a brief prison sentence 25 years ago for conspiring to prescribe and distribute laetrile, has been reprimanded in connection with the death of a patient. Privitera, who practices in Covina, California, states that he specializes in "allergy, nutrition, chelation, clot detection, darkfield microscopy, toxicity testing, mineral testing, and immunity testing . His Web site also describes him as an "internationally acclaimed researcher, author, and leading authority on natural, nontoxic alternative therapies" and "a pioneer in darkfield microscopy."

Laetrile is a quack cancer remedy In 1975, Privitera was convicted of conspiring to prescribe and distribute it and was sentenced to six months in prison. In 1980, after the appeals process ended, he served 55 days in jail but was released after being pardoned by California Governor Jerry Brown. Then, because Privitera been prescribing unapproved substances for the treatment of cancer, the California Board of Medical Quality Assurance suspended his medical license for four months, placed him on ten years' probation, and prohibited him from making any representation that he was able to cure cancer through nutrition. During this period, he developed a bogus diagnostic test called live blood analysis and marketed equipment for doing it .

Wilson B. The rise and fall of laetrile. Nutrition Forum 5:33-40, 1988.

Antineoplastons, 95 biologically guided chemotherapy, 118 Essiac, 73 Immuno-Augmentative Therapy (IAT) 133-135 laetrile, 103-104 ozone infusion, 114 vitamin C, 121

Antineoplastons, 96-97 biologically guided chemotherapy, 117 dietary treatments, 20-21, 45, 48, 55-58 Gerson treatment, 45, 48 herbal treatments, 71, 74, 80-81 Immuno-Augmentative Therapy, 142-143 Kelley regimen, 55-58 laetrile, 104-106 macrobiotics, 65-66 Pau D'Arco, 87 vitamin C, 122

adjunctive treatments, 229 Antineoplastons, 93-95 biologically guided chemotherapy, 119-120 eumetabolics, 113 Gerson treatment, 49 herbal treatments, 69, 80-81 hydrazine sulfate, 15, 21, 100-101 Immuno-Augmentative Therapy (IAT) 22, 142-149 insurance eligibility and, 177-178 Iscador, 86 laetrile, 21-22, 104-105, 106-107 Livingston-Wheeler regimen, 110 radiotherapy, 9 vitamin, C, 21, 122-125, 126

Antineoplastons, 93-97 best case, 23, 25, 51, 97, 142, 231-233 biologically guided chemotherapy, 116-117, 118 Federal role, 6, 199,203,205; see also National Cancer Institute, Food and Drug Administration Gerson treatment, 47-50 herbs, 72-73, 77-81, 84-86 Hoxsey treatment, 77-81 hydrazine sulfate, 100-102 imagery and visualization 35-38 Immuno-Augmentative Therapy (IAT) 132, 148 147 168, 230-231 information on, 25 insurance eligibility and, 177-178, 185-186, 189-190 192 Iscador, 84-86, 87 Kelley regimen, 56 laetrile, 103-107, 201-202 Livingston-Wheeler regimen, 110-111 macrobiotics, 64 meditation, 34 pharmacologic and biologic approaches, 83 psychological/behavioral approaches, 33 vaccines, 110-111 vitamin, C, 120, 121-122, 122-127 wheatgrass regimen, 41 see also Clinical trials

Alliance for Alternative Medicine, 173 American Medical Association, 168, 187 Antineoplastons, 95-97, 232 best case, 23, 25, 97, 142, 231-233 biologically guided chemotherapy, 118-120 dietary treatments, 48-50, 55-58, 6~66, 229 Gerson treatment, 48-50, 232 herbal treatments, 74, 80-81, 86 history, 4-5 Hoxsey treatment, 80-81 hypnosis, 36-37 Immuno-Augmentative (IAT), 132, 140-147, 168, 230-231, 234-235 insurance eligibility and, 177-178, 185-186, 189-191 Kelley regimen, 55-58 laetrile, 21-22, 103-107, 201-202, 232 Livingston-Wheeler regimen, 110-111 macrobiotics, 64-66 multifaceted treatments, 22 pharmacological and biological approaches, general, 228-229 psychobehavioral approaches, 14, 10, 20, 36-37 radiotherapy, 9 vitamin, C, 22, 122-127, 232-233 see also Clinical trials; Effectiveness; Pre-clinical testing; Quality control

Antineoplastons, 92, 219 dimethyl sulfoxide, 99 herbal treatments, 69, 75 hydrazine sulfate, 100 Immuno-Augmentative Therapy, 131, 142, 143, 145, 147, 148, 192 information dissemination, general, 154, 162, 163-164, 166, 167 insurance reimbursement, 186-192 (passim), 195 laetrile, 21, 22, 192, 201-202 Nieper, Hans, 112, 173 ozone infusion, 114

Labeling, 112, 173, 208 Ladas, Harold, 116 Laetrile, 6, 14,18,21-22,47,99,102-107, 155, 162,192, 201-202, 212

Antineoplastons, 92 biologically guided chemotherapy, 118 database, 153, 161, 163 dimethyl sulfoxide, 99 herbal treatments, 69, 74, 78, 80-81 Immuno-Augmentative Therapy, 131, 139, 140, 141, 142, 145, 148-149, 234 information dissemination, general, 153, 161-163; see also Cancer Information Service insurance eligibility, 186, 191 laetrile, 21-22, 103, 105-107, 232 Medicare, 187

Antineoplastons, 14, 91-97, 157, 162, 182, 183, 194, 206-207, 210, 219, 323 biologically guided chemotherapy (Revici), 14, 115-120, 169, 173-174, 202, 203, 220-221 conventional, 9-10 costs, 179-180, 181, 184 dimethyl sulfoxide, 14, 99-100, 222 evaluation of, general, 5, 228-229 FDA approval, 19 hydrazine sulfate, 15, 21, 100-102, 163 Immuno-Augmentative Therapy, 4, 8, 15, 19, 22, 131-149, 153, 162, 168, 173, 182, 183, 192, 211, 230-231, 234-235 laetrile, 6, 14, 18, 21-22, 47, 99, 102-107, 155, 162, 192, 201-202, 212 Livingston-Wheeler regimen, 14,41, 107-111, 183, 211-212 Medicare coverage, 186-187 Nieper, Hans, 14, 104, 111-115, 169, 173 Revici, Emanual, 14, 115-120, 169, 173-174, 202, 203, 220-221 see also Chemotherapy; Immunological system; Food and Drug Administration: specific vitamins

Antineoplastons, 95 biologically guided chemotherapy, 118 Essiac, 73, 74-75 Immuno-Augmentative Therapy, 133-136, 137, 139 laetrile, 103-104 ozone infusion, 114 vitamin C, 121 see also Animal research

Antineoplastons, 94-95, 96-97 biologically guided chemotherapy, 116-117, 118, 119, 120 clinical trials, 23 Immuno-Augmentative Therapy, 134, 135, 140 information on, 16, 26 laetrile, 104, 105 vitamin C, 121, 122

criminal practices, 26 Federal Government, relations with, 6, 210, 211-212 Gerson treatment, 43, 215 Kelley regimen, 54 Immuno-Augmentative Therapy, 131, 136, 140, 211 lnsurance coverage, 188-189, 191, 192, 193 laetrile, 102, 201, 202 see also Disciplinary measures, practitioners; Licenses and permits; Litigation

Antineoplastons, 93 dimethyl sulfoxide, 99-100 herbal treatments, 69, 87 Immuno-Augmentative Therapy, 139, 140, 234-235 laetrile, 103, 107 Livingston-Wheeler regimen, 110 selenium, 118, 119 vitamin C, 122

The law that created Medicare prohibits payment for services or items that "are not reasonable and necessary for the diagnosis or treatment of illness or injury" (Social Security Act, Section 1862(a)1, 42 USCA 1395y (1)(A)). As interpreted by HCFA, a treatment is considered medically reasonable and necessary if it has been generally accepted by the professional medical community as effective and safe for the condition being treated . Colonic irrigation, cellular therapy, and laetrile are among the medical procedures or items HCFA does not consider to be reasonable and necessary; therefore, they are not currently covered by Medicare (221).

Act Section 1861(t), USCA 42 Section 1395(t), CCH 1223, 3115, 1988). Drugs and biologics used for indications other than those approved by FDA may be covered as long as FDA has not ruled that such use is unapproved specifically, and as long as other reimbursement criteria are met (221). Coverage is not available for drugs, such as laetrile, that are marketed without FDA approval (45 Fed. Reg. 110, June 5, 1980).

While HCFA clearly prohibits coverage for some unconventional cancer treatments, such as colonic irrigation, cellular therapy, and laetrile (221), policies for other unconventional cancer treatments are not stated explicitly.

Travelers show. In these cases, the policy-holders claimed they expected reimbursement for laetrile and nutritional therapies because these treatments were "reasonable and necessary" for the treatment of their cancer.

However, the judges in these cases did not find this argument convincing, because it was demonstrated that the patients knew prior to treatment that neither laetrile nor nutritional treatments were considered to be effective by the American oncologic, medical, or regulatory communities. In both these cases, the patients had signed informed consent forms or affidavits (to obtain laetrile) stating that the treatments were not FDA-approved or were not considered effective by the majority of physicians (37,304,734).

Similarly, in Shumake v. Travelers the court ruled that the insurer had to reimburse for laetrile and vitamins, because they were determined to be medically necessary in accordance with the terms of the insurance policy.

This is distinguished from "health fraud," in that it does not necessarily involve false or unsupported claims of a treatment's effectiveness.) U.S. third-party payers allege that several unconventional cancer clinics and at least one billing service company have committed what falls into the category of insurance fraud, but the prevalence of fraudulent claims is unknown. Many fraudulent claims submitted for unconventional cancer treatments request reimbursement for "chemotherapy." A minority of unconventional health care providers treat patients with chemotherapeutic regimens that are recognized by the medical community (321). Unconventional cancer treatment claims have also been submitted for chemotherapy or "non-toxic chemotherapy" followed by a set of initials; for example, "chemotherapy AMGL" has been used to represent laetrile treatments. Third-party payers disagree about whether such claims deliberately misrepresent the services rendered, thus constituting fraud, or simply reflect the clinic's definition of their treatment. In this and all other possible identifications of fraud, the pattern of claims submissions ultimately determines if an individual is deliberately and knowingly committing fraud (250,320,856,908).

More sophisticated insurance fraud often involves billing service consultants familiar with numerical coding systems used by providers and insurers in the United States. Two of the coding systems used are the International Classification of Diseases (ICD —9th revision) and the Current Procedural Terminology (CPT —4th edition). The ICD codes represent various diagnoses and CPT codes denote the treatment administered to the patient. If the CPT code is an appropriate match for the ICD code, the insurer will generally approve coverage without further investigation. Billing companies that allegedly commit fraud give the unconventional treatments CPT codes that not only match the ICD code for the patient, but also represent accepted medical treatments. For example, treatments that are not covered under the terms of the policy, such as coffee enemas or laetrile, might be coded as a type of chemotherapy, which would be covered under the contract (228,321). Claims submitted in this manner appear on paper to be valid, and some insurers believe many fraudulent claims of this type go undetected by their claims departments (228,320,321).

I received much the same treatment in 1976 from the sociology department at a major university when I presented the cultlike characteristics of the laetrile community and asked for help in investigating it. The sociologists felt there was little difference between the society of medical scientists and the society of laetrile advocates.

We now see a new use of an ancient tool used by experts at manipulation of the public mind. Even the words "holistic," "alternative," "complementary," "unconventional," and "unorthodox" are invented euphemisms intended to mislead. They are benign terms covering a vast array of practices—most of them unproved, dubious, disproved, absurd, and fraudulent. Any politician knows one must find an enemy, even a straw one, to win elections. The term, "slash, burn, and poison' was invented by laetrile advocates to demean ethical cancer medicine, and it worked and it stuck.

Traditionally, a distinguishing feature of quacks has been this: If they cannot prove their claims scientifically, they use the popular press and lobby for special privilege in legislatures. Twenty-seven states legalized laetrile in the 1970s and 1980s. Seven states have passed "access to medical treatment" (AMT) bills. These allow any licensed practitioner to practice any method within the legal scope of practice --proved or not—on any patient, provided "informed consent" is obtained. Regulatory boards, organized medicine, and public-service agencies oppose such bills. (Even now the Texas board is considering liberalizing regulations on aberrant practices to conform to policies resembling AMT bills.)

One quick test for the usefulness of an "alternative" therapy is to ask oneself, what would happen if this therapy were tomorrow no longer available? How much would acupuncture and homeopathy be missed? How about antineoplastons, immunoaugmentive therapy, laetrile, and unsupervised megavitamins? If the public had never heard of them, the common health would not suffer a bit. On the other hand, how would the public handle absence of antibiotics, X-rays, anesthesia, and major operations?

Next, she turned to a popular herbalist in her community who treated her with herbal remedies for about six months without avail. She then went to Mexico for laetrile.

Several weeks later, she asked her husband to take her home because laetrile, too, had failed. Her husband looked after her for more than a year before the lesion became so gross and her pain so unbearable that she asked to be taken to a doctor for the first time. She died five days later.

He stated that he knows where she went wrong, and that if he gets cancer, will use the dietary treatment correctly. He continued to operate the health-food store, send people to the herbalist, and advocate laetrile.

Distortion of perspective. Without proper perspective, people can be made to "strain out gnats and swallow camels." Unable to tell good from bad, some people shun "toxic" chemotherapy, but swallow cyanide (laetrile).

During the 1970s, the very fabric of our sound consumer protection law was seriously threatened by laetrile promoters who attempted to legalize its use. Fortunately, although about half the states passed laws permitting its sale, federal laws blocking interstate distribution were not changed. After the FDA won a protracted court battle, the use of laetrile within the United States became minimal.

Participants in Manner's June 1988 seminar also received information on the "Manner 5" program, which Manner said was intended to augment the basic program with 21 days at the clinic plus 69 days of treatment at home. Its components included laetrile, various enzymes and supplements, an "anti-viral compound in the same class of interferon," a "lysing agent . . . designed to dissolve, decompose and disintegrate cancer cells," orange capsules to add oxygen to the blood, white-and-brown "antifermentation" capsules to "keep the carbon dioxide level in the blood low," and white-and-blue "antifibrinator" capsules that "strip cancer cells of their protective cocoon." Although literature referred to Manner 5 as "a new program that we feel will revolutionize cancer therapy," Manner said the program has been used for about five years and that the clinic's medical director, Gilberto Alvarez, recommended it for all cancer patients.

The Manner Clinic also offered a "prevention program," which consists basically of the first week of the cancer therapy, but laetrile was omitted from the slow-drip infusion.

At the Texas seminar, Manner frequently cited the theories of John Beard, who published a book on the enzyme treatment of cancer in London in 1911, and of Ernst T. Krebs Sr. and his son, Ernst Jr., who embraced Beard's ideas and advocated laetrile therapy.

Amygdalin (laetrile)

Manner entered the public spotlight in 1977 by announcing at a National Health Federation seminar that he had cured cancer in mice with injections of laetrile, enzymes and vitamin A. The experiment was published in 1978 in a chiropractic journal .

. known only to me and a few friends. When I have 100 of these files, I'm going to put them in a package, to take them to Washington, D.C., and I think the whole laetrile controversy will be over." However, the alleged files and Manner's intent to send them to Washington were not mentioned again in any of the dozens of subsequently published materials distributed at the Texas seminar.

The mechanisms of claimed effects are relatively unimportant here, but the time scale for effects should be taken into account: some proponents claim that their treatments have direct cell-killing effects, which may happen rather quickly (e.g., laetrile, Hoxsey tonics), while for other treatments that claim to work by building and stimulating the patients' immune systems, the effects are described as more gradual (e.g., macrobiotics, IAT).

One way to determine whether a treatment has anti-tumor effects is to test it in a phase II trial. Given a treatment that has been used by hundreds or thousands of patients, however, is there another way of efficiently generating some, at least preliminary, information before a prospective trial is contemplated? NCI's laetrile case review (274), described in chapter 5, was an attempt at this. The results were disappointing because a relatively small number of evaluable cases were submitted, but still, valuable lessons were learned from it about laetrile and about the method itself. This "best case" approach, with modifications, could be used more prominently in determining which might deserve further investigation. One element that may be crucial to the success of a best case review is the active participation, or at least support, of the unconventional practitioner.

It is important to note that a best case review is not the end of the evaluation line; some cautions must be kept in mind. This type of study cannot, except possibly in exceptional cases, provide definite proof of efficacy in terms of life extension, nor any estimate of rate of response to the treatment. In addition, the concerns expressed in the report of NCI's laetrile review are relevant: the possibility of falsified information being used, omission of information, either intentional or unintentional; other mainstream or unconventional treatment that may have been used by the patient without the unconventional practitioner's knowledge; the possibility of mistaking the natural variability of cancer for true regression; and the possibility of "spontaneous regression." This last point is worth pursuing a little further.

It is worth noting that two instances of "otherwise unexplainable regressions" have been described in chapter 5 of this report. One of the NCI-file patients in the laetrile review, who had had no treatment, was deemed to have had a partial remission (274); and the only long-term survivor in the first Mayo Clinic vitamin C study was a pancreatic cancer patient who had both subjective and objective evidence of lessening disease (though tumor status itself was not reported), and who was taking the placebo.

Specific unconventional cancer treatments were highlighted as examples of fraudulent treatments (e.g., laetrile and IAT). Legal, fiscal, and sociological aspects of health fraud were discussed (658,988).

CCS, founded in 1973 by two former IACVF members, is currently one of the most active organizations advocating the use of unconventional cancer treatments. Based in California, it has approximately 5,000 members. In a spring 1988 mailing, CCS stated that its purpose is "public education in the prevention and control of cancer and other diseases through nutrition, tests, and non-toxic alternative therapies." The same flier cites laetrile; Gerson, Hoxsey, and Koch enzymes; wheat grass; immunology; mega-vitamins and minerals; detoxification; nutrition; dimethyl sulfoxide (DMSO); and chelation therapy as examples of the treatments considered "non-toxic" by CCS (166).

Formerly known as the Committee for Freedom of Choice in Cancer Therapy, CFCM, a California-based organization, describes itself as "committed to freedom of choice with informed consent for physicians and patients in medicine" (365). CFCM sponsors informational seminars on alternative cancer treatments and distributes generally positive information about specific treatments. CFCM is one of the oldest politically-active advocacy organizations in this field, beginning in the 1970s with lobbying efforts to legalize laetrile (365). At one time, there were 500 CFCM chapters nationwide; now there are approximately 50, the decrease due apparently to changes in the legal status and waning popularity of laetrile (54).

Amygdalin is a glucoside found in the kernel or seeds of many fruits and is frequently referred to as "Laetrile" or "Vitamin B-17." While some of the proponents have recommended it for the treatment and control of cancer, FDA has never approved these claims. There are no published clinical studies that demonstrate that laetrile is safe and effective and cancer patients who take it sometimes forgo conventional therapies to their detriment.

Last summer, FDA and DOJ, with the assistance of FTC, sought a temporary restraining order, preliminary injunction, and permanent injunction against the marketing of unapproved new drugs by three corporations and one individual. The products, laetrile, in injectable and tablet form, and apricot seeds, were promoted as cancer treatments through their Internet websites. Despite FDA warnings to these companies in 1998, they continued to promote their products as remedies for cancer. In January 2001, District Court Judge Shelby Highsmith entered a Consent Decree of Permanent Injunction in this case with regard to defendants World Without Cancer, Health Genesis Corporation, and David E. Arjona. The preliminary injunction and Consent Decree of Permanent Injunction required the defendants to cease using the websites to promote the sale or offer for sale their laetrile products.

The Rise and Fall of Laetrile

Laetrile Spammers Facing $631,585 Penalty

Laetrile Spammers (Christian Brothers) Facing $631,585 Penalty

This is somewhat analogous to the laetrile review, which ended with very little evidence in support of the treatment. With laetrile, a decision was made to proceed with a clinical trial anyway, because of the public health importance of doing so at the time. (At the time, laetrile had been legalized in more than 20 States, and was in widespread use, which was not the case with IAT.)

(Laetrile is a quack cancer remedy.) In 1980, after the appeals process ended, he served 55 days in jail but was released after being pardoned by California Governor Jerry Brown. (The pardon occurred in response to a letter-writing campaign generated by the National Health Federation, a group that espouses what it calls "health freedom.") Then, because Privitera had been prescribing unapproved substances (including laetrile, calcium pangamate, and DMSO) for the treatment of cancer, the California Board of Medical Quality Assurance suspended his medical license for four months and placed him on ten years' probation under board supervision. During the probationary period, Privitera was "prohibited from making any representation that he is able to cure cancer through nutrition." He was also forbidden to tell patients they had cancer unless the diagnosis was confirmed in writing by an appropriate board-certified specialist. During the probationary period, Privitera commercialized live-cell analysis and founded two companies that marketed devices for doing it. Silent Clots mentions that in 1993, a federal judge signed an order authorizing Internal Revenue Service agents to enter his clinic premises to effect a levy and that a seizure was made. However, the book provides no further details about his tax-related difficulty.

A special case has been made that patients with ''terminal'' disease should have ready access to quack remedies. The argument is appealing but specious. Should swindlers be allowed to "comfort" terminal patients by selling them phony stock—telling them it will make them rich before they die—on the theory that they don't need their money anyway? Moreover, even if it were possible to pinpoint the terminal state (which it usually is not), there is no way to open the door for one group of patients without opening it for others. The Supreme Court recognized this fact when it ruled unanimously in 1979 in a laetrile case that no exception to the 1962 efficacy law should be made for so-called terminal cancer patients. Congress, the high court ruled, had not intended to protect only those suffering from curable diseases.