Wallace F. Janssen
Report
Food and Drug Administration 5600 Fishers Lane Rockville, Md. 20857
The Cancer "Cures": A Challenge to Rational Therapeutics "Quackery kills a larger number annually of the citizens of the United States than all the diseases it pretends to cure." So wrote an American physician in 1861, in an unsigned article published in the National Quarterly Review. In the context of the times, the golden age of quackery, this was not an extreme statement. One Samuel Thompson had explained the situation in his "New Guide to Health", first published in 1822. " T h e people," he said, "regard it among their vested interests to buy and swallow such physick as they in their sovereign will and pleasure shall determine, and in this free country denounce all restrictions upon quackery as wicked monopolies for the benefit of physicians." Thompson's highly popular guide promoted his patented system for treating all diseases by means of heat, herbal laxatives, and emetics. T h o m p sonianism spread like wildfire, dominating medical practice for decades, especially in the Southern and Western States, and undoubtedly killing many thousands, b u t finally becoming discredited and replaced by other theories of healing. Today we are in the midst of another nationwide health fad, the Laetrile panacea for all forms of cancer. When it has run its course, as it inevitably will, people will look back with amazement t h a t so many were so gullible at a time when reliable health information was readily available. Why is it t h a t the American public seems to learn so little from experience in the area of health? Something must be lacking in health education. This.article.nolt subject to U.S. Copyright Published 1978 American Chemical Society
We can vaccinate successfully against infectious diseases b u t not against the lure of a painless, easy, but worthless t r e a t m e n t for cancer. One reason, no doubt, is t h a t today's generation has no memory of the conditions t h a t resulted in enactment of the nation's laws to ensure drug safety and effectiveness. Significant but forgotten is the fact t h a t it was a fake cancer t r e a t m e n t which led Congress to pass the first Federal law against false claims for drugs. In 1910 the Bureau of Chemistry (now FDA) attempted to prosecute
the promoter of Dr. Johnson's Mild Combination T r e a t m e n t for Cancer. At the time everyone thought the new Food and Drugs Act of 1906 would do away with the thousands of worthless and dangerous " p a t e n t medicines" then on the market, a major public health problem. But the Supreme Court ruled in the Johnson case t h a t the law did not prohibit false "therapeutic" claims on drug labels but only false statements about the identity or composition of drugs. Justice Oliver Wendell Holmes, Jr., son of the famous American poet and physician, who wrote the majority
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"The people . . . denounce all restrictions upon quackery as wicked monopolies for the benefit of physicians."—1822 opinion, could not believe Congress intended to legislate in the complex area of therapeutics. He concluded t h a t Johnson could not be prosecuted for "mistaken praise" of his treatment, even though the indictment charged t h a t he knew his claims were false. Justice Charles Evans Hughes, one of three dissenters, thought just the opposite. T h e law prohibited labeling t h a t was "false or misleading in any particular", and Hughes believed Congress meant what it said. In his view the courts had been made responsible for determining from the evidence whether or not a drug was misbranded. He saw the Holmes decision as opening the door to every kind of quackery, which indeed it did. President Taft a t once called on Congress to close this dangerous gap in the law. What he said applies as much today as in 1912:
Congress responded with the Sherley Amendment, which made it a crime to label drugs with false and fraudulent claims of therapeutic effectiveness. Unfortunately, the words " a n d fraudulent" made it difficult for the Government to prosecute, in many cases, because it was necessary t o prove the défendent intended to swindle the purchaser. Twenty-six years later, in 1938, Congress passed a new food and drug law which eliminated the so-called "fraud joker" and required scientific proof of safety before a new drug could be sold. And in 1962 the Congress voted unanimously for even stronger drug controls which required effectiveness as well as safety to be established before a drug goes on the market, a milestone advance in medical history. Opposition to the legislation continued in the courts, but in 1973 the Supreme Court unanimously upheld the law and the FDA's enforcement program.
"There are none so credulous as sufferers from disease. T h e need is urgent for legislation which will prevent the raising of false hopes of speedy cures of serious ailments by misstatement of facts as to worthless mixtures on which the sick will rely while their disease progresses unchecked."
A tremendous improvement in the quality and reliability of drugs has resulted from the drug effectiveness law. In the area of prescription drugs, for example, more than 6800 products have been removed from the market since 1962 because of the lack of evidence t h a t they were effective, and the labeling of some 2000 others has been
Chemical analysis of "Chamlee's Cancer Specific" from a "Pacific island shrub" showed only alcohol, water, and small amounts of iron, strychnine, and saccharin. Ads such as this appeared until the 1930's when stronger laws and rigorous enforcement put an end to them 198 A · ANALYTICAL CHEMISTRY, VOL. 50, NO. 2, FEBRUARY 1978
changed to reflect today's medical knowledge. Even more important, the law made the drug manufacturers responsible for proving the merits of their products, rather than requiring the Government to go into court in each case to show t h a t a drug was misrepresented or unsafe. B u t it was the unproven cancer t r e a t m e n t s t h a t demonstrated most strikingly the need to establish effectiveness of drugs before allowing them on the market.
The Koch Treatment—Distilled Water T h e great cancer swindle of the 1940's and early 1950's, and one of the greatest medical hoaxes of all times, was promoted by William F. Koch, M.D., of Detroit, who did business as the "Christian Medical Research League". Dr. Koch's t r e a t m e n t was a bonanza. Analysis showed it to be distilled water of extraordinary purity, but Dr. Koch claimed it contained 1 part of its alleged active ingredient, the chemical glyoxylide, in 1 trillion parts of water! A Federal prosecutor said this dilution was like dumping a cocktail into the Detroit River and expecting to get a kick from the water flowing over Niagara Falls. There was no evidence t h a t glyoxylide had any therapeutic effect. B u t a great many people believed in it—over 3000 health practitioners across the nation paid $25 per ampul for it, and charged patients as much as $300 for a single injection! In 1942 the Federal T r a d e Commission, seeking evidence to ban Dr. Koch's advertising as false and misleading, held hearings in 21 cities. Local practitioners who testified ranged from reputable doctors who were misled by the advertising to fakers with no medical training whatever. In 1943 the FDA prosecuted Dr. Koch. T h e trial lasted 18 weeks. Forty-three expert witnesses testified t h a t the Koch products were misbranded and not effective in the treatment of cancer or any other disease. T h e defense had 104 witnesses who said the products were efficacious in the t r e a t m e n t of 69 different diseases, from acute appendicitis to herpes zoster, with special emphasis on cancer, tuberculosis, and coronary thrombosis. After 9000 pages of testimony (2 250 000 words) the case went to the jury, which deliberated 8 days without reaching a verdict, and was dismissed. A poll of the jurors showed three who had insisted on acquittal from the outset. H u m a n credulity had again been shown to be a major factor in the success of quackery. Dr. Koch was tried again in 1946, but after five months a juror became ill and a mistrial was declared. In 1948, after an FDA inspection of
Koch's laboratories, he announced he was retiring and went to live in Brazil. For a time the business was continued by Koch's associates under the name of the Christian Medical Research League. A product known as t h e "Koch T r e a t m e n t " continued to be sold in Mexico long after it disappeared in the United States. Harry Hoxsey's Herbal Tonic T h e biggest health hoax of the 1950's was the Hoxsey T r e a t m e n t for internal cancer. There were two products: the "pink medicine" composed chiefly of lactated pepsin and potassium iodide, and the "black medicine" composed of a common laxative (cascara) in an extract of prickly ash bark, buckthorn bark, red clover blossoms, barberry root, burdock root, licorice root, pokeweed, a n d alfalfa. Harry Hoxsey, in his ghost-written book, "You Don't Have to Die", attributed this 1840 formula to his great grandfather whose horse was said to have recovered from a leg cancer after grazing in a pasture where such plants were growing. Apart from the laxative and potassium iodide, which have no value for cancer, all of the ingredients had long been discarded for any medical use. Hoxsey was a medicine man all his life. After being prosecuted for violating the medical practice laws of several states, he finally set up a "clinic" at Dallas, Tex., where the judge of the Federal Court was a believer in "the t r e a t m e n t " even though his wife had died of cancer after using it. T h e Hoxsey Clinic offered a package deal consisting of a perfunctory examination by a salaried osteopath and some routine blood and urine tests, after which the patients were told they had cancer and then the t r e a t m e n t was prescribed. This cost $400 for a lifetime supply of the two medicines. At the peak of the business over 10 000 people were getting the medicines. Hoxsey had a large income from oil leases as well as the clinic, and he fought the Government both in the courts and with publicity. Writers and editors were paid to publish pro-Hoxsey articles. A "crusade of prayer" launched a write-to-Congress campaign against the FDA. Nevertheless, the medicines were found worthless by two Federal Courts after lengthy trials, one before a jury. In preparing for the litigation, FDA inspectors investigated some 400 cases of persons who were claimed by Hoxsey to have been cured of cancer by the treatment. T h e results formed a typical and significant pattern: One group of these victims had diagnosed themselves or had never had a biopsy showing they had cancer.
"There are none so credulous as sufferers disease."—1912 A second group had cancer and had been treated for it by accepted and effective methods, but had later gone to the Hoxsey Clinic fearing they had not been cured. T h e remaining cases were people who had received the Hoxsey treatment and had died of cancer (the majority) or still had it. No case of a bona fide cure was found. Public warnings issued by the FDA saved thousands from being victimized; in 1960, after 10 years of litigation, a Federal Court injunction finally stopped the sales of the Hoxsey t r e a t m e n t in the United States. Announcing the conclusion of the case, FDA estimated t h a t cancer patients had paid over $50 million for the drugs. How many had paid with their lives was unknown. B u t like the Koch treatment, Hoxsey's medicines continued to be offered by practitioners in Mexico. Krebiozen—Mineral Oil Injections While the FDA was battling the Hoxsey treatment, another very different cancer drug was also making headlines and converts. This was Krebiozen, an alleged investigational drug said to be manufactured from the blood serum of horses inoculated with a mold t h a t causes a disease known to veterinarians as "lumpy jaw". Unlike Harry Hoxsey's backwoods herb remedy, Krebiozen had an aura of high scientific prestige. It was sponsored by the famous Dr. Andrew C. Ivy of the University of Chicago, who had joined forces with Stephan and Marko Durovic, Yugoslav immigrants, who said they made their discovery in Argentina. Ivy's announcement and endorsement of the drug at a lay press conference in 1951 was greeted with indignation by his university colleagues, the scientific community, and the American Medical Association, which regarded him as a defector from respectable science. B u t Dr. Ivy's prestige gained widespread confidence and credibility among cancer patients. To many he became a hero battling for humanity against the "Medical Trust". A book would be needed to tell the entire story of Krebiozen. Thousands of cancer victims eagerly sought it, and thousands of doctors prescribed it as an investigational drug at $9 per ampul—billed as a "donation". But the cancer experts who suspected Krebiozen from the beginning were vindicated in 1963 when a team of FDA chemists, analyzing the only sample
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of the substance ever obtained from the sponsors, found it to be creatine monohydrate, an amino acid present in all animal tissue and without value in the t r e a t m e n t of cancer. At the same time, analysis of the drug as packaged for injection into patients showed t h a t only mineral oil was present! Krebiozen inspired an emotionally charged, organized following of people who were convinced t h a t the scientific establishment was suppressing the use of a drug which could save lives. Nevertheless, when the FDA became convinced t h a t the law had been violated, Dr. Ivy, the Durovics, and their Krebiozen Research Foundation were prosecuted. A Federal grand jury investigation resulted in an indictment on 49 counts of fraud and conspiracy to carry out a gigantic hoax. But on J a n uary 31,1966, after a nine-month jury trial at Chicago, all defendants were found not guilty. Later, an investigation of jury tampering led to the conviction of one of the jurors, who served a six-month prison term. T h e acquittal verdict meant t h a t the Government had failed to prove deliberate action to defraud the public. It had no bearing on the lack of scientific evidence on the effectiveness or safety of Krebiozen, nor did it change the fact that the ampuls contained only mineral oil. Interstate distribution continued to be illegal. On March 28, 1966, the first of a series of demonstrations and "sit ins" by Krebiozen supporters blocked access to the FDA Commissioner's office. On succeeding days the group beseiged the H E W Secretary and their representatives in Congress to make the FDA back down and allow the continued shipment of Krebiozen. H E W officials held a public meeting with the group to hear their protest and explain the Government's position, but to no avail. Eleven U.S. Senators called for another start in determining whether the drug had any value for cancer. T h e pressure was intense. But the FDA did not back down. T o have done so would have meant t h a t for every cancer patient who thought he was helped, there would be many others who could lose their lives by stopping, or not getting, effective treatment. FDA's Commissioner, Dr. James L. Goddard, put it this way: " I know there are several hundred people who believe in their hearts t h a t Krebiozen will cure them. And
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"The sponsors . . . have held out false hope to unknown numbers of cancer victims . . ."—1966
I have deep sympathy for these people. B u t there are 198 million people whose health and safety depend in some measure on the integrity of FDA . . . . T h e sponsors of krebiozen have not fulfilled the requirements of the laws passed by the Congress for the introduction of safe and effective drugs to the American public. T h e y have held out false hope to unknown numbers of cancer victims . . . . T h e Commissioner of Food and Drugs has neither the moral nor the legal right to disregard the laws of Congress and the evidence of science. We cannot and will not permit the introduction of Krebiozen into interstate commerce." Like believers in the Hoxsey Treatment, Krebiozen advocates demanded a "fair test" of the drug. B u t Dr. Ivy had never submitted evidence sufficient to demonstrate the existence of an active substance. Animal test data—essential to justify FDA clearance of an investigational drug—were totally inadequate to justify tests in humans. Yet, in 15 years of illegal distribution as an investigational drug, Krebiozen was tried on thousands of cancer patients—with no credible effects. A National Cancer Institute committee of 24 leading cancer experts reviewed 504 case histories provided by Dr. Ivy and found unanimously t h a t Krebiozen was ineffective as an anticancer agent. W h a t happened afterward? T h e Krebiozen boom collapsed. Stephan Durovic abruptly left the United States, via Cuba, to Paris, and then to Switzerland where he had banked his profits. Marko Durovic, the lawyer brother, spent years in controversy with the Internal Revenue Service. He died in 1976. And Dr. Ivy continued to dispense Krebiozen from his office in Chicago, changing the name to "Carcalon", which he claimed to be an improved product, and which he continued to prescribe until retirement a year ago.
Miscellaneous, But Remarkable T h e Koch, Hoxsey, and Krebiozen treatments overlapped in time, and there were numerous other cancer frauds during the 30-plus years t h a t saw their rise and fall. Most remarkable was the fact t h a t so many believed in them.
Mucchoricin, extracted from moldy decayed wheat, was made and sold by Philip Drosnes, a former tire salesman, and Lillian Lazenby, an excafeteria worker, who opened a "clinic" at Detroit. Promoted as an "antibiotic", it had a bacteria population which made it a dangerous drug as well as an ineffective one. T h e Sanders treatment, offered by an Oklahoma motel operator, kept his 70-unit facility running at capacity, day after day. It was made of ground warts from horses, in a sour milk suspension. Millrue, an herbal extract with iron and vitamins, was prescribed and dispensed by Roy Paxton, an Illinois healer, who diagnosed all diseases by feeling the patients' feet. After serving a three-year sentence for violating the Federal Food, Drug and Cosmetic Act, he became a director of the National Health Federation, the leading advocate of quackery under the slogan "freedom of choice". Orgone energy, the nonexistent universal force imagined by psychiatrist Wilhelm Reich, exploited hundreds of cancer victims who rented "orgone accumulators" for $250 per month. Patients sat inside the box-like devices to absorb the "orgone". T h e Rand Vaccine, a sensation in 1966, was much more effective as a stock promotion than as a cancer treatment. T h e Rand Development Corp. supplied it free of charge, but the stock of the company leaped from $7 to $50 a share and then fluctuated widely. In J a n u a r y 1967 the Securities and Exchange Commission suspended trading, and J a m e s H. Rand was subsequently indicted for stock fraud. T h e "vaccine" was crudely made from the blood of animals which had been injected with material from h u m a n cancers collected indiscriminately from hospital operating rooms. Extensive publicity from stories planted in newspaper financial pages and a national magazine brought thousands of cancer patients to Ohio physicians and hospitals, where the "vaccine" was generally thought to be a legal investigational drug. T h e one obstacle to nationwide distribution was the Federal Food, Drug and Cosmetic Act. An application to FDA to show t h a t the vaccine was reasonably safe for use in man failed in every respect. Investigation disclosed toxic ef-
fects, heavy bacterial contamination, and in one study (not disclosed by the sponsor) t h a t the vaccine actually hastened the growth of cancer in test animals. On February 7, 1967, on evidence provided by the FDA, a Federal Court order stopped further manufacture and distribution, and a few weeks later Rand consented to a permanent ban after a full hearing. T h e stock fraud indictment was dismissed. T h e reaction to the ban was intense. Public sympathy was aroused by press headlines—"Court Ban Like Death Sentence", "Cancer Victims Fight For Hope"—but the facts did not permit a retreat. Organizations and individuals who had backed Krebiozen now backed the Rand treatment. In a week after the ban a petition with 25 000 signatures was being circulated in Washington urging t h a t supplies of the vaccine be continued. T h e tragic stories of those who had been duped were ignored. But the Rand " c u r e " declined almost as quickly as it had arrived.
And Now—Laetrile Today's cancer fad is Laetrile, also known as amygdalin and vitamin B-17. It is heavily promoted by wellorganized groups who are using all the mass-communication techniques. T h e product is different, but the claims (to prevent cancer as well as treat it) are as extreme and dangerous as those used pre-1912. FDA's Laetrile file begins with a memorandum of a visit by a Mrs. Mo.riarity to the Chicago district office on November 30,1945. She had come to tell the Agency t h a t a Dr. Ernest T. Krebs, M.D., of San Francisco, had a new drug which had cured her of cancer. T h e FDA was not impressed by this testimonial; cancer "cures" were a dime a dozen. But some 16 months later inspectors interviewed Dr. Krebs, his son E. T. Krebs, Jr., and a Dr. Gurchot. T h e drug they were shipping, for cancer, was not Laetrile b u t "Mutagen", a brand name for chymotripsen, an enzyme derived from the pancreas of cattle. In 1952 the FDA learned t h a t Dr. Krebs had a different cancer treatment, made from apricot kernels, which he first called "Lyotral", and which was not yet available even for investigational use. But soon it was learned t h a t a p a t e n t had been granted and was being used to promote the drug in California. T h e first Federal action against Laetrile came in 1960 when an interstate shipment was seized from an osteopath who had taken over the operation of the Hoxsey Cancer Clinic at Dallas, Tex. There was no contest. T h e record shows t h a t immediately after the clin-
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". . . with a little luck, proper timing and a good promotion program, a bag of asafetida with a unique chemical side chain can be made to look like a wonder drug".—1977 •
ic was enjoined from using the Hoxsey t r e a t m e n t they had switched to Laetrile. T h e second Laetrile case was a criminal prosecution of three Los Angeles practitioners for shipping the drug illegally to a lay person in Idaho. T h e Government charged t h a t the new drug, labeled for investigational use, was not shipped to "an expert qualified by scientific training and experience to investigate the safety of said drug", as required by law. Two of the three defendants were M.D.'s past 80 years of age. T h e y consented to a court order to stop distributing the drug. T h e third defendant was the notorious medical con-man, Roy De Welles, whose main business was promoting enemas for the t r e a t m e n t of all diseases. A warrant for his arrest was never served, the reason being t h a t he was being prosecuted in the Federal Court at Indianapolis for mail fraud. Convicted, he served a 10-year prison sentence. T h e Krebs, father and son, did business as the " J o h n Beard Memorial Foundation". In the third FDA legal action involving Laetrile, the Krebs and their Foundation were charged with shipping another new drug which had not been cleared as safe under the law. This was an alleged "Vitamin B15", also known as "pangamic acid". It was claimed to be effective as a heart stimulant and for improving the performance of race horses. In this case, E. T. Krebs, Jr., and the Foundation pleaded guilty to five counts of violating the new drug law, and a total fine of $3 755 was imposed. Krebs, Jr., was put on probation for three years, on condition t h a t he would not ship any new drugs, including Laetrile, without approval from the FDA. A supply of Laetrile already manufactured was permitted by the court to be sent to the McNaughton Foundation of Montreal, Canada, for research purposes. At this point two things happened: First, a promotional paperback book, "Laetrile—Control for Cancer", appeared in newstands, book stores, and thousands of health food stores across the country. Second, Laetrile, which had never been legally available in the United States, became readily available in Canada and Mexico. Neither of these developments
could be dealt with by the Food and Drug Administration. Publicizing of the t r e a t m e n t in the press, dangerous as it is to desperate, frightened cancer victims, is protected by the first amendment to the Constitution. And the prescribing and dispensing of drugs in other countries is, of course, beyond the reach of U.S. law. This leaves, as the only means available to protect U.S. consumers, the authority of the Government to bar the importation and interstate distribution of illegal drugs.
The Laetrile Challenge T h e significant difference between the Laetrile craze and its predecessors is the power of the promotion behind it and the damage it threatens to the laws which insure drug safety and effectiveness. Laetrile has become a cause célèbre, promoted by both organized quackery and its misguided followers. T h e situation has been aptly described as an "unhealthy alliance of promoters, fighting for the right to cheat, and victims fighting for the right to be cheated". T h e slogan of the movement, "Freedom of Choice", is b u t one side of a counterfeit coin. T h e other side is freedom for swindlers to sell worthless drugs to desperate victims who will pay any price and clutch at any straw. For many the consequences are fatal—because the lure of easy, painless t r e a t m e n t for cancer is irresistible. T h e "sit-in" demonstrations by Krebiozen followers in 1966 were a preview of the pressures applied to State legislatures by Laetrile lobbyists, beginning in 1976. T o date, 13 States have enacted laws to "legalize" the drug by stopping enforcement of their drug and medical practice laws. More serious are bills in the Congress to repeal the effectiveness requirements of the 1962 Drug Amendments. Some 125 House members and four Senators have endorsed this legislation. It seems incredible in the light of the legislative history of the 1962 law, enacted unanimously by the Congress, t h a t so many members have gone on record against its most import a n t requirement. T h e hearings held by Senator Kefauver disclosed t h a t false claims for prescription drugs were hardly less prevalent and no less dangerous than those for the so-called " p a t e n t medi-
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cines" at the turn of the century. As one witness p u t it, "If an automobile does not have a motor, no amount of advertising can make it appear to have one. On the other hand, with a little luck, proper timing and a good promotion program, a bag of asafetida with a unique chemical side chain can be made to look like a wonder drug." To this we can add t h a t placebo effects and mass hysteria make the promotion of cancer panaceas the easiest of all drug swindles. Consumers, law makers, and even many physicians can be blinded to the consequences. As another witness pointed out at the hearings, the average practicing physician just does not have the time, facilities, skill, or training to be an expert on drug safety. Without an agency to assure safety and effectiveness, every physician would have to be his own Pasteur, and the American people a willing army of guinea pigs. T h e Supreme Court of the United States in 1973 upheld specifically and in great detail the FDA's powers to administer the 1962 drug effectiveness law. Yet in 1977, a U.S. District Court Judge ordered this Agency to stop action against the distribution of Laetrile. Incredibly, this decision presumes the 296 judges of Federal District Courts qualified to make the final judgments on medical policy and products. We have not seen the last of the Laetrile issue. It is a fundamental challenge to the credibility of science and the future of rational therapeutics.
Wallace F. J a n s s e n is FDA historian and author of numerous articles on FDA activities. Previously as FDA's information chief, he was primarily involved with problems of health misinformation and quackery. Janssen was instigator of FDA's public warning which saved more than 6000 persons from being victimized by the Hoxsey cancer treatment.
