Dr. Richard Klausner, the new NCI director, has called for the development
of what he calls "non-natural products" to fight cancer (see p. 1). To
us, this is moving NCI even further in the wrong direction. As some NCI
scientists have already shown, there are compounds found in natural products
that confirm their long folk usage in the fight against cancer. The NCI
should step up its investigation of these agents, especially the non-toxic
ones, not only for cytotoxic (cell-killing) ability, but even more importantly
for their immune-enhancing ability. This should form a major portion of
the NCI budget.
By now, almost everyone has heard about the anticancer activity of a
few toxic plants. Taxol of course has been the wonder drug of the 90s—now
largely run out of steam. It is derived from the bark of the Western yew
tree (Taxus brevifolia) and is FDA approved for use in the treatment of
ovarian and breast cancer.
Many readers will also be aware of the so-called vinca alkaloids (Vincristine
and Vinblastine), which are derived from a European creeping plant, called
the periwinkle (Vinca rosea).
In addition, drugs called epipodophyllotoxins (e.g., Etoposide and Teniposide)
are derived from mandrake or Mayapple (Podophyllum peltatum).Many other
anticancer drugs are products of the type of aerobic bacteria called Streptomyces.
These include such well-known agents as Bleomycin and Doxorubicin.
PLANTS ARE USEFUL
So the principle that plant-derived chemicals can be useful against
cancer is hardly controversial. And Dr. Klausner could plausibly argue
that much of the work on these treatments was done at NCI. However, we
would rejoin that all of these agents are bound by the limitations of
chemotherapy. The agents all work by poisoning normal and cancer cells
alike, and hopefully the cancer cells at a faster rate than the normal
ones.
Predictably, all of these agents cause significant toxicity in patients,
sometimes worse than that seen synthetic agents. This has long been known.
In fact, records show that Mayapple was even used by some American Indians
to commit suicide!
By contrast, most of the herbal treatments we discuss in this issue
either work by mechanisms other than straight cytotoxicity, i.e., through
immune enhancement, detoxification, or some unknown mechanism. They all
lack the obvious, harmful side effects of cytotoxic drugs.
Contrary to current dogma, it is not necessary for a treatment to cause
major toxicity in order for it to be of therapeutic benefit to cancer
patients.
Furthermore, these non-toxic agents can often be administered by the
patients themselves or by their primary care givers, and do not require
the input of subspecialists at NCI-funded comprehensive cancer centers.
In fact, sociologically, they move treatment in the opposite direction
that NCI has opted for--towards greater patient empowerment. Could this
be on of the reasons for the resistance of NCI to this type of development?
Yet despite NCI foot-dragging on natural agents, the exploration of
healing plants, is now moving to the forefront of interest around the
world. Although this may seem startling to scientists in the US, such
treatments are and always have been favored by four-fifths of the world's
population. Is everybody else crazy?
For example, in China and Japan the use of Traditional Chinese Medicine
(T.C.M.) or kampo grows apace. There has also been a renaissance of interest
in ancient Indian (Ayurvedic) concepts. In Canada, what treatments are
more popular than Essiac tea or 714X (which is made, in part, from camphor).
Pau d'arco and cat's claw are enormous popular in Latin America
MUSHROOM TREATMENTS
In addition, various kinds of mushrooms have been used medicinally since
antiquity. In the fourteenth century, Chinese physician Wu Rui wrote that
the common shiitake mushroom (now the second-best-selling mushroom in
the United States) was a beneficial treatment for various kinds of malignancy.
According to the Hungarian scientist L. Réthy, mushrooms have
long been used in what he called "shamanistic therapy." And one of their
principle medicinal uses in this regard has been in treating tumors.
LANDMARK STUDY
In 1969, a landmark scientific study was performed by Dr. Tetsuro Ikekawa
of Purdue University and his colleagues at the National Cancer Center
Research Institute in Tokyo (the "Japanese NCI"). First they collected
wild mushrooms in Japan, prepared water extracts, and then tested them
for anticancer activity.
Mice, implanted with sarcoma cells were given injections of these water
extracts. The results were quite astonishing. But although they came from
an American university they were far more appreciated in Japan (e.g.,
75.3 percent tumor inhibition with oyster mushrooms, 80.7 percent with
shiitake and 81.1 percent with shiitake white powder. Cure rates were
somewhat lower, but still impressive.)
As these statistics indicate, the cure rate was highest with shiitake.
The doctor isolated what he felt was the active component of the mushroom—a
white powder containing non-toxic chemicals called polysaccharides. This
powder performed even better than crude mushrooms, actually curing a total
of 66 percent of the mice tested!
One of these polysaccharides was isolated in the following year. It
was dubbed Lentinan, after the Latin botanical name of this mushroom,
Lentinus. This has became one of the top-selling anticancer agents in
Japan, where it is approved as an adjuvant treatment for stomach cancer.
And in fact, as little as 1 milligram per kilogram body weight of Lentinan
totally regressed tumors in 100 percent of the mice.
Although results in humans have not been this good, it still remains
a useful agent. Lentinan was very actively researched in Japan after this.
Scientists found that Lentinan works by stimulating T cells (thymus-mediated
cells); these in turn activate another kind of defense cell, the macrophage
(Shikoku Acta Medica 1984;40:473-478). Because of this ability, Lentinan
has been used routinely in Japan to protect carp from lethal bacterial
infections.
Lentinan has also been found to stimulate natural killer (NK) cell activity.
According to a large body of research, NK cells can puncture the outer
membrane of cancer cells through their production of an enzyme called
perforin. This puncturing leads to the death of the unwanted cancer cell,
as was neatly illustrated a few years ago in Scientific American (Jan
1988:38-44). And, unlike interleukins or tumor necrosis factor, Lentinan
can kill cancer cells without causing any serious side effects in the
patient.
Lentinan, however, is not available in the US. However, since lentinan
is just one polysaccharide out of many found in the shiitake (and polysaccharides
themselves are just one class out of many natural chemicals in medicianal
mushroom) patients can obtain the same or better effects by consuming
whole mushrooms, or by taking more balanced extracts. These are widely
available.
Another branch of mushroom research has centered around the maitake
(or "dancing") mushroom. Our friend Dr. H. Nanba of Tokyo has published
data in peer-reviewed journals showing that taken orally maitake has even
greater anticancer activity than shiitake. In recent years, he has focussed
his activity on developing the so-called "D fraction" of maitake, which
may be the single most potent polysaccharide found to date in the anti-cancer
mushrooms. These are now in clinical trial at a midwestern cancer center.
PLANTS OF FIELDS AND WOODS
There are a great many herbs found in fields, forests, roadways, wastelands—probably
even in the Maryland backyards of some NCI researchers—that have
been explored for their anticancer potential.
Of course, NCI has a well-publicized Natural Products Division. But
despite some important work done, most of the products already known to
have anticancer activity have never really been clinically tested. And
when they are, those tests can be pathetic.
For instance, pau d'arco tea is a well-known Andean cancer treatment.
NCI scientists focussed their attention on one purified chemical found
in pau d'arco, lapachol. Finally, after years of activity, they got to
the point of conducting a clinical trial. But the trial was cancelled
when the drug didn't show effects after just five days!
By contrast, when Latin American scientists studied lapachol, they did
so for years, understanding that it works by methods more subtle than
rapid cytotoxicity. They showed that in advanced cancer it took a full
two years for lapachol to have significant activity, as it did in three
out of eight patients. Tests of natural products must be conducted with
understanding, sympathy, and sensitivity to how such agents are used by
folk healers.
How could NCI seriously respect Asian or Latin American practices, however,
when they have never shown even the most passing interest in our own North
American folk traditions? They have joined with the AMA and the ACS in
branding these are mere quackery.
For almost 100 years they have condemned the multi-herb formula of the
late Harry Hoxsey. The now-departed Office of Technology Assessment (little
mourned in these parts) once tried to suppress a contract report on Hoxsey
which pointed to the positive data on these herbs. Yet his formula contained
pokeweed root (Phytolacca americana), source of a well-known immune modulator.
Isn't it interesting that the governor of colonial New York wrote to Benjamin
Franklin that he had found pokeweed root to be the traditional Mohawk
Indian treatment for cancer?
Does it intrigue them that Japanese scientists have independently isolated
a powerful "antimutagenic B factor" in burdock? Enough to do some serious
research?
Dr. Klausner, our advice would be that before you start your search
for millions of "nonnatural natural" agents, you carry out an independent
clinical trial of what is still the nation's oldest established cancer
treatment, the Hoxsey herbal remedy. Perhaps you yourself would lead a
site visit to the Hoxsey clinic in Tijuana, and the other clinics down
there, to at least listen to patient stories. Such a trip would be an
earnest of your sincerity for years to come.
And what about Essiac? This is a mixture of four common herbs from the
Ojibwa Indians of Canada, given to nurse named Rene Caisse in the 1920s
as a cancer remedy. Dr. Klausner, thousands of North Americans are now
taking this. Can you say whether it works? There are no published, clinical
studies on this mixture, although I have seen some preliminary NCI studies
on both cancer and HIV infection that look promising. So before we go
off looking for millions of new compounds, how about a sympathetic yet
independent study of Essiac tea conducted by qualified scientists?
DOZENS OTHERS SHOW PROMISE
In addition to these famous formulas, Dr. Klausner should be aware that
there are quite a few other promising developments in the herbal field.
Around the world, thousands of people are already taking these treatments.
So why not find out what is happening to them? Many of these have potential
as anticancer agents. Some of them have been in use for millennia. Don't
they now deserve some serious attention from NCI?Many examples can be
found in the standard literature.
I would suggest that Dr. Klausner study a book in the celebrated Peterson's
Field Guides' series, Eastern/Central Medicinal Plants by Steven Foster
and James A. Duke (1990). This is a tremendous work of scholarship and
offers suggestions of the tremendous scope from the world's herbal and
natural traditions. (Readers should be aware that many herbs and plants
are TOXIC. Refer to the above book for particulars.) As examples:
Soapweed (Yucca glauca) is a blue-green perennial growing
from 2 to 4 feet on dry soils from Iowa to Texas. Indians used the poulticed
soapweed root on inflammations and water extracts have anticancer activity
against a type of melanoma (B16). No clinical trials performed.
Jimsonweed (Datura stramonium) is a folk remedy for cancer.
But reader, beware! It is violently toxic and causes severe hallucinations.
Promising as a drug.
Horseradish, the condiment, experimentally has shown anticancer
activity "as science has come to expect from the mustard family" say
Foster and Duke.
Common nightshade (Solanum nigrum L.), in leaf-juice preparations,
have been used in folk lore as an external remedy for tumors. Some varieties
contain solanine, which is poisonous.
Bloodroot (Sanguinaria canadensis L.) is a member of the poppy
family. It is one of the herbs in the aforementioned Hoxsey formula.
Its alkaloid sanguinarine has been shown to have anticancer activity.
Indian Hemp (Apocynum cannabinum L.) contains cymarin and
apocymarin, which have shown anti-tumor activity. The latter compound
raises blood pressure.This plant contains cardiotoxic glycosides and
is poisonous.
CommonPlantain (Plantago major L.) The leaves and
seeds, widely used around the world, are a folk remedy for cancer in
Latin America. It is said to stimulte healing.
Pale Indian Plantain (Cacalia atriplicifolia L.), found in
dry woods and openings from Jersey to Georgia,was used by Indians as
a poultice for external cancers.
Field or wild mustard (Brassica rapa L.) are used on burns.
This contains factors, such as isothiocyanates, that NCI itself suggests
may prevent certain cancers.
Greater celandine (Chelidonium majus L.) Found in waste places.
(I once found it growing as a decorative plant in an NIH office—the
scientist had no idea of its medicinal value.) This is a prominent folk
remedy for cancer in Russia and neighboring countries. Conjugated with
the drug thiotepa, it becomes Ukrain, an experimental European anticancer
medication of promise.
Elecampane (Inula helenium L.) found in fields and roadsides,
it is used in China to treat certain cancers. A strong sedative, it
contains alantolactone, which happens to be a good, less-toxic deworming
agent.
Sneezeweed (Helenium autumnale L.) was used as snuff by American
Indians. Helenalin, a lactone, was found to have significant anti-cancer
activity by NCI itself.
Wild ginger (Asarum canadense L.) whose root was used by American
Indians for indigestion. It contains the antitumor compound aristolochic
acid.
Common Milkweed (Asclepias syriaca L.) is a folk cancer remedy,
potentially toxic. should be used with care.
Wild or spotted geranium (Geranium maculatum L.) found in
the woods from Maine to Georgia. The root is used externally as a folk
remedy for cancer.
Dr. Klaunser, these are just examples of dozens of such potentially
useful treatments in the natural world. A more intensive discussion of
a few of these is given in the following pages [i.e., on this Web site].
