LAETRILE - Part 1
The most enduring legacy of the meteoric rise of laetrile to a place of preeminence among unconventional therapies for
cancer during the 1970s may well be sociological and political, rather then medical in nature. Laetrile spawned a popular
movement for freedom of choice in health care decisions spanning the ideological spectrum that probably has not been
seen in this country since the time of Harry Hoxsey. Though it had been in use for at least 25 years as a therapy for
cancer, it is estimated that at any given time during the mid-1970s, 70,000 people were using laetrile as a cancer
treatment, for pain control or as a preventive measure.
In the debate over broader philosophical and political issues, the critical question for cancer patients, whether or not
laetrile is an effective therapy for cancer, was largely overshadowed, though clearly laetrile has not lived up to the
expectations of many of its most ardent advocates.
According to journalist Michael Culbert, D.Sc., founding member of the laetrile advocacy group Committee for Freedom of
Choice in Cancer Therapy, Inc.: I decided very early that the issue was neither scientific nor medical but political. And that issue was--is--simple: What
right does the state have, or should it have, to intervene in the medical decisions between a patient and his doctor,
particularly if that patient is dying of a "terminal" disease for which there is no known, or guaranteed cure?
Ralph Moss, a key figure in the laetrile controversy in the 1970s, has been a leading critic of the cancer orthodoxy, as well
as the political and economic forces he believes drive it, since leaving his position as Assistant Director of Public Affairs at
Memorial Sloan-Kettering Cancer Center (MSKCC) in 1977. Moss was fired for aligning himself publicly with a group of
MSKCC employees who believed the public was being given inaccurate information on the outcome of animal studies of
laetrile's effectiveness. Moss provides a detailed account of the laetrile controversy and his experience at MSKCC in his
book The Cancer Industry. Moss states the medical issue this way: Laetrilists are not just advocating a single substance
but, like the advocates of other unorthodox therapies, are proposing a new kind of treatment for the patient's body and mind.
There is apparently an irreconcilable difference between laetrilists and orthodox doctors in how they understand cancer.
Since the time of John Hunter (1728-1793), orthodox physicians have tended to see cancer as a localized disease that,
as Hunter said, "only produces local effects." Such a disease would therefore be curable through localized means--for
example, removing the growth through surgery.
...Experiments in this century, and particularly in the past thirty years, have suggested that the body has natural immune
mechanisms against cancer analogous to those that function in microbial infections. The corollary of this view is that
cancer can be controlled by enhancing the body's normal immune functions, which orthodox methods tend to
destroy.
The typical "metabolic therapy" often advocated by proponents of laetrile includes megadoses of vitamins A and C,
minerals such as selenium, and enzymes, particularly pancreatic enzymes. And, in order to free these enzymes to act
upon cancer cells, practitioners often recommend limiting intake of animal protein. Alcohol, coffee, soft drinks and
processed foods may also be proscribed. Finally, some form of engagement with the psychological and spiritual aspects
of the illness is often encouraged, as well.
"Laetrile" is a term often used interchangeably with "amygdalin" and "vitamin B-17." Amygdalin was first isolated from bitter
almonds by two French scientists in 1830. "Laetrile" is a term coined by Ernst T. Krebs, Sr., and Ernst T. Krebs, Jr., in
1953. It is a contraction of laevo-rotary mandelonitrile beta-diglucoside, a purified form of amygdalin that turns polarized
light in a left-handed ("laevo") direction. The Krebses believed that this quality was a vital aspect of the substance's
effectiveness against cancer. Amygdalin contains two glucose, or sugar, molecules linked to the compound mandelonitrile,
whereas laetrile contains one sugar molecule.
"Laetrile" (with a capital "L") usually refers to the Krebses' original product, whose purification process was patented by
them; "laetrile" (with a lower case "l") refers to the commercial form of amygdalin which is most likely a mixture of the left
and right-turning forms, which the Krebses believed to be much less effective as a therapy for cancer.
In 1970, Krebs, Jr., advanced the theory that cancer is a vitamin deficiency disease that can be prevented by laetrile,
which he dubbed vitamin B-17. Critics of his theory charge that this was an attempt to circumvent FDA regulations
which apply to medicines but not vitamins, and also that amygdalin does not meet the definition of a vitamin, since it has
not been shown to be required to maintain health and no disease has been associated with its absence.
However, according to Culbert: [The cyanide-bearing sugar compounds] are so widespread in nature that Krebs, the earlier McNaughton Foundation (...a
research apparatus for the development of laetrile) and the late Dean Burke Ph.D., the peppery biochemist who for years
headed the cytochemistry division of the National Cancer Institute, decided that altogether they constituted one or a
complex of B vitamins--which they agreed should be the 17th in the order of definition: Vitamin B-17.
They argued that ubiquity in nature of such compounds was a proof, but not the only proof, of their vitamin nature. Their
essential non-toxicity and solubility in water are other characteristics, Dean Burke always argued, that added to their
B-vitamin status. But the crux of the vitamin argument was whether or not their absence or depletion led to a pathological
condition. For the laetrilists, their absence or depletion did indeed lead to a pathological condition: cancer. Not only that,
but laetrile and its breakdown products are involved in a host of other metabolic processes.
Laetrile is a glycoside, a family of substances commonly found in plants, including chick peas, lentils, lima beans,
cashews, brown rice and millet. Commercially, laetrile is derived from the kernels of the apricot, peach or bitter almond.
Glycosides can be split into one or more molecules of sugar and a non-carbohydrate substance in reaction with water,
usually facilitated by an enzyme.
Laetrile breaks down in the body into glucose, benzaldehyde and hydrogen cyanide.
Cyanide is toxic to both cancerous and non-cancerous cells. Benzaldehyde, which has also been isolated from burdock,
one of the constituent herbs in the Hoxsey therapy, has shown anticancer activity in some animal tests.
McCarthy in a 1982 review in Medical Hypotheses classifies benzaldehyde
as a potential cytologic cancer therapy which "retards cancer growth by intervening selectively in the disordered control
mechanisms responsible for malignant behavior, without producing direct cytotoxicity."
Amygdalin taken orally has been known to be a poison since ancient times, though amygdalin-laden black and brown
bitter seeds were described as antitumor agents in the pharmacopeia of ancient China. Egyptian, Greek, Roman
and Arabic physicians also used amygdalin to treat tumors.
It was postulated by Ernst Krebs, Sr., that laetrile killed cancer cells selectively through the action of the enzyme
beta-glucosidase. According to Krebs' theory, the enzyme splits amygdalin to release cyanide, which kills nearby cells.
Krebs asserted that cancer cells are killed selectively because beta-glucosidase is more abundant in cancerous tissues
and also because cancer cells are deficient in another enzyme, rhodanese, which promotes rapid breakdown of
cyanide.
Krebs' theory concerning the action of laetrile is very controversial and not accepted by most researchers. An anonymous
article entitled "The Committee for Freedom of Choice" published in a 1993 issue of CA - A Cancer Journal for Clinicians,
an American Cancer Society publication, disputes Krebs' assertions on the basis that animal tissues contain only trace
amounts of beta-glucosidase and that rhodanese is present in equal levels in cancerous and non-cancerous
tissues.
According to Glenn D. Kittler, the first documented "successful" use of laetrile with cancer was reported in 1951 by Arthur
T. Harris, M.D. of Los Angeles. Prior to the 1970s, laetrile was used as a therapy for cancer
primarily by Hans Neiper, M.D., in Germany and Ernesto Contreras, M.D., in Mexico. Contreras, who runs the Clinica del
Mar in Tijuana, has been treating patients with laetrile since the early 1960s and continues to do so today. Contreras has
never published his outcomes with laetrile, but claims modest results. According to Contreras, 35 percent of patients
(most of whom have already failed conventional therapy) do not respond to the therapy. Of the remainder, half experience
temporary arrest of their cancers. Among the other half are "more definite responses," ranging from slight improvement to
disappearance of symptoms. Contreras estimates that perhaps five percent of the patients are "saved."
Some evaluations of laetrile's effectiveness were conducted during this period, as well. Moss describes a 1953
retrospective study of 44 cancer patients by the California Cancer Commission that for many years was the definitive
anti-laetrile study. The Commission claimed that laetrile was "completely ineffective" in humans, laboratory animals or in
vitro, though the report later came under attack for omitting physician reports of subjective benefit to patients and a
discussion of "toxic cellular changes" in cancer cells that were mentioned in the original laboratory studies. Critics also
noted that doses of laetrile given patients were very small compared to those considered by practitioners to be
therapeutic.
Nevertheless, during the ensuing years, growing numbers of patients used laetrile and some papers did appear
supporting its effectiveness. In 1962, John A. Morrone, an attending surgeon at the Jersey City Medical Center, reported
"dramatic relief of pain" in ten patients treated with laetrile, as well as indications of tumor regression.
In the 1966 report, Proceedings of the Ninth International Cancer Congress, Rossi cites a ten-year trial in Europe
involving 150 patients that found "50 percent of all cases in treatment showed objective improvement" and concluded that
laetrile was "an extremely useful chemotherapeutic drug."
Animal studies carried out in several different laboratories under NCI sponsorship in 1957, 1960, 1969 and 1973 showed
negative results. Several sources of laetrile were used in a variety of rodent tumor systems, both with and without beta
glucosidase. Other investigators testing laetrile alone or with beta glucosidase in animal systems also found no
antitumor activity. Laetrile has also been tested alone and in combination with beta glucosidase in nude mice with
human breast and colon tumor xenografts. In its summary of the animal research on laetrile in the report
Unconventional Cancer Therapies, the Office of Technology Assessment (OTA) reports that no activity was found in any
of these tests.
However, Moss describes three animal experiments using laetrile not mentioned in the OTA report that did have positive
results. The first was carried out by the SCIND Laboratories in California in preparation for an Investigational New Drug
Permit (IND) application being filed by the McNaughton Foundation in 1970. In their second study on carcinoma of rats
(Walker 256) with intraperitoneally injected amygdalin, the mean survival time of controls was 23 days, while the mean
survival time of the amygdalin-treated group was 38 days, a 70 percent increase. Every amygdalin-treated rat survived
longer than every control animal. Moss quotes Dr. Carl Baker, then director of the NCI, as saying in a letter to
Congressman Edward Edwards, "The data provided by the McNaughton Foundation certainly indicates some activity in
animal tumor systems."
Further, animal studies conducted in Europe also demonstrated some activity. Dr. Paul Reitnauer, Chief Biochemist of the
Manfred von Ardenne Institute in Dresden conducted a test in which 20 of 40 H-strain mice were given bitter almonds in
addition to their standard diets. Fifteen days after the initiation of the diet, all the mice were inoculated with 1 million
Ehrilch ascites cells. The 20 control mice lived an average of 21.9 days following the injection, while the 20 mice receiving
the bitter almonds lived an average of 25.8 days, a statistically significant difference.
Finally, Moss reports that Dr. T. Metianu, director of research in pharmacology-toxicology at the Pasteur Institute in Paris
conducted a study using an adenocarcinoma model with mice. Ten mice given subcutaneous amygdalin lived an average
of 58 days past the time of tumor take, whereas ten controls lived an average of 21 days. A repetition of the experiment
resulted in an average 47 day survival for treated mice and 27 day survival for controls.
The early 1970s saw growing numbers of patients seeking out laetrile as a cancer therapy and it was during this time that
the laetrile became the focus of a large-scale political movement, as well. In June 1972, John Richardson, M.D., an
Albany, California physician whose used laetrile in his rapidly-expanding practice, was arrested for violating state laws
intended to curtail its use. Richardson was a member of the conservative John Birch Society, and its membership rallied
around the issue. The three trials of Richardson galvanized a national movement for freedom of choice in medical
therapies, and the original Committee for Freedom of Choice in Medical Therapy, Inc. ballooned into a nationwide
movement in all 50 states with a membership estimated at 20,000 to 50,000 members.
In July 1973, Dean Burke, while still working with the NCI, wrote to Congressman Robert A. Roe that laetrile had been
successful in NCI directed studies using the Lewis mouse lung cancer model while the agency consistently denied its
efficacy.
1975 was a pivotal year in the controversy over laetrile. In that year a U.S. District Court judge barred the FDA from
preventing patients from securing their own supplies of laetrile from foreign sources. Later that same year, federal officials
conducted a crackdown on the importation of laetrile into this country. Sixteen people, including Robert Bradford, now
affiliated with the American Biologics clinic in Tijuana, were arrested or indicted on charges of smuggling laetrile from
Mexico. The principles were eventually found guilty in a lengthy trial, though no prison time was meted out.
It was also during this period that the largest series of animal tests with laetrile was carried out by Chester Stock and
colleagues at Memorial Sloan-Kettering Cancer Center in New York and Catholic Medical Center of Brooklyn and Queens.
One of the investigators, Kanematsu Sugiura, conducted six initial experiments in mice with spontaneous mammary tumors
and found that laetrile showed no significant prevention of growth of primary tumors, but did show an inhibition of lung
These tests were followed by a series of five experiments designed to replicate Sugiura's initial work. Two blinded
experiments were conducted in which tumor status was assessed in such a way that observers did not know which mice
received laetrile and which were controls. This second set of tests did not confirm Sugiura's original findings. The authors
concluded that "laetrile was found to possess neither preventive, nor tumor-regressant, nor antimetastatic, nor curative
anticancer activity."
One key difference between the two studies was the method of evaluation--Sugiura used visual gross examination plus
microscopic slides, the standard approach at the time, while the second study employed a bioassay technique. In the
latter, the lungs of the experimental mice were shredded and injected into other mice; if tumors developed at the injection
sites, it was an indication that lung metastases were present.
These tests at MSKCC are extensively chronicled in Moss' book, The Cancer Industry. Sugiura was a respected senior
researcher at MSKCC and believed, along with some other researchers, that transplantable tumors in mice were not really
representative of human cancers. Sugiura was enthusiastic about the potential of laetrile to inhibit metastases, and his
initial studies were encouraging.
In his book, Moss, at that time an employee at MSKCC, describes political forces at the esteemed research institution that
he believes led the administration, initially receptive to the idea of evaluating laetrile and other unproven therapies, to
repudiate Sugiura's promising research and, in Moss' opinion, to issue public statements concerning laetrile research at
the institution which were misleading. Moss left his position in public affairs at MSKCC as a result of the controversy and
went on the become a prominent proponent of open evaluation of unproven methods. In personal communications with
Moss, Sugiura maintained his belief until his death in 1979 that laetrile was effective against cancer in the animal systems
he studied: I still think my experimental results on the effect of amygdalin (with high doses) on spontaneous mammary tumors
(adenocarcinomas) are correct- stoppage of growth of small tumors temporar[il]y; prevent the development of lung
metastases 80 percent against 20 percent in the control group (saline); delayed the development of spontaneous
mammary cancers for three to four months.
According to the article in CA - A Cancer Journal for Clinicians, patient records submitted by practitioners were analyzed
by committees of the California Medical Association and the California Department of Public Health. Also, the FDA and NCI
conducted a joint investigation of 12 case histories submitted by Dr. Ernesto Contreras. In all of these case reviews, it was
concluded that no therapeutic effect was demonstrated. But as is often the case in reviews of this kind, pathologic proof of
malignancy was missing in many cases and in others patients had received conventional therapy as well.
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