NOTE: This article is provided as general background information on a new avenue in cancer research. Nothing that you read here should be taken as an endorsement of any particular approach or clinic. For more information on this particular topic, see the article on trophoblasts and hCG in the February, 1997 Chronicles.
Recent discoveries by scientists worlds apart have unexpectedly breathed
new life into an old view: the trophoblastic theory of cancer.The first scientist
is Valentin I. Govallo, MD, PhD, director of the Laboratory of Immunology
in Moscow. Govallo is the author of 290 scientific articles and 20 books,
including The Immunology of Pregnancy and Cancer (1993).
The second is M. Rigdon Lentz, MD, PhD, currently the chief of hematology
and oncology at the Comprehensive Cancer Center of Valdosta, GA. Before this
year, neither scientist knew of each other's work.
In Govallo's 1993 book, first published in the United States, he explains
that he arrived at his ideas through a study of the immunology of spontaneous
abortions. In 1972, he started treating such miscarriages, which are a major
problem for many Russian women. Because of some similarities between pregnancy
and malignancy, Govallo began a program of treating cancer patients. His
first attempts involved stimulating their immune systems, through the use
of vaccines and drugs. Although at a fairly low technological level, it was
a program that in many ways resembled that of NCI's Steven Rosenberg.
Govallo was disappointed, however, when he discovered that this led to only
two long-term survivors out of 66 patients treated. The rest died of their
cancer. Govallo reached the conclusion (not yet acceded to by NCI immunologists)
that "stimulating the functions of T lymphocytes in blood is not enough to
induce an efficient anti-tumor immunity."
According to Govallo, the reason for the failure was that the tumor itself
was hindering the activity of the immune system, emitting certain "blocking
factors." This was a theory first proposed by orthodox scientists in the
late 1960s. (It is also an integral part of Dr. Lawrence Burton's
Immunoaugmentative Therapy, or IAT, practiced in the Bahamas since the late
1970s.)
Since some of these blocking factors seem to bear striking resemblance to
those emitted by an embryo during pregnancy, Govallo had the brilliant idea
of using a placental extract to immunize the patient against the fetus-like
cancer.He found that an extract of what is called human chorionic villi (see
illustration), when added to a test tube of white blood cells, "effectively
blocks all reactions of cell immunity."
More than a decade ago, Govallo began injecting a hypdermic needle worth
of this extract under the skin of cancer patients, once every two to three
months during the first year and then again, as needed. Sometimes, this extract
caused "fever, shivering, and light weakness" but these symptoms generally
disappeared within 24 hours. Otherwise, the treatment was non-toxic. He calls
this "immuno-embryo-therapy."
A glance at the statistics shows that the results reported in his book are
startling: a 77.1 percent five-year survival rate. From his account, these
were all advanced cases, no longer responsive to surgery, radiation or
chemotherapy. Govallo himself admits that "it is not exactly clear how the
placental extract effect works."
So far the reaction from the U.S. medical community has been blasé.
Last year, the publisher (Nova Scientific of Commack, NY) sent copies of
Govallo's scientific text to every major medical journal in the country.
To date, however, only one has reviewed it. In the Maryland Medical Journal
(42:500-501, 1993), Joseph M. Miller, MD wrote: "If the results are accurate,
this innovative approach could be one of the greater discoveries of the twentieth
century."
He adds that "the book should be read with hopeful anticipation and not accepted
as dogma." Fair enough. But, to date, no one in the U.S. cancer establishment
has expressed the slightest interest in attempting to duplicate his results.
THE ULTRAPHERESIS MACHINE
Dr. M. Rigdon Lentz has also spent two decades investigating the ability
of cancer to turn off an otherwise-normal immune system. Attempting to
physically remove blocking factors, he custom built a machine that filters
them out of the cancer patient's bloodstream, using a technique called
UltraPheresis (comparable to kidney dialysis). In the late 1980s, Lentz
carried out FDA-supervised Phase I and Phase II studies, removing plasma
fractions with low molecular weights from the blood. Unlike Govallo, who
sees a few Russian patients a month, Lentz is not currently treating patients
with his method, as the objective of the earlier trials was scientific
knowledge. Additional funding would be required to proceed with more extensive
Phase III studies.
In the prestigious Proceedings of the National Academy of Sciences,
Lentz and colleagues identified, purified, and characterized immune system
inhibitors found in the blood of cancer patients. These were identified
as receptors for tumor necrosis factor (TNF) (PNAS 87:8781-8784, 1990;
also, Cell 61:361-370, 1990). By producing this factor, the tumor is apparently
able to deactivate the body's otherwise powerful immune response to foreign
tissues. The discovery of this "anti-TNF" is an exciting scientific finding,
with implications for the treatment of a number of different diseases.
Lentz's published results contain many revelations about the ultimate
power of the immune system, once it is deblocked, to destroy tumors.One
of the most startling facts is that the first three of Lentz's terminally
ill patients who died in the initial clinical trial had tumor lysis syndrome:
dead cancer cells and debris that can overwhelm the liver and kidneys
(J Biol Response Mod 8:511-527, 1989). Autopsies of these patients showed
that "all measurable disease" had been destroyed due to "massive hemorrhagic
and coagulative necrosis." Lentz learned that one must proceed slowly
in harnessing such explosive anti-cancer reactions.
Patients receiving UltraPheresis also experienced intense, if transient,
pain in their primary tumor and metastases. There was also fever, which
Lentz brought down with the drug, acetaminophen (Tylenol®).Sixteen
patients were treated between June, 1985 and April, 1986. As noted, three
(18.7%) died after rapid tumor breakdown. A general improvement in physical
condition and sense of well-being was seen in 65% of the cases, accompanied
by improved appetite & weight gain.
"An objective reduction in tumor of 50 percent or more was observed
in 6 of the 16 [remaining] patients," Lentz wrote (37.5 percent). Although
this was not a study of survival per se, Lentz noted that 9 of the 16
patients survived more than one year, and 6 of the 16 for more than two
years. (Two are alive, eight years later.)
Despite such promising results in terminal cases, again there has been
little interest in the cancer establishment (of which Lentz is a card-carrying
member) to vigorously explore this innovative approach because, he says,
of its complexity.
INVASION OF THE TROPHOBLASTS
What is most surprising in all this is the new life Govallo and Lentz
have unintentionally breathed into an old theory of cancer. The trophoblastic
thesis was first put forward in 1902 by the Scottish embryologist, John
Beard (Lancet 1:1758). Beard was rigorously trained in Germany and became
lecturer in embryology at the University of Edinburgh, one of the world's
great medical schools. His pioneering work on the embryology of fish and
other vertebrates led him to contemplate the phenomenon of cancer. He
was among the first to notice that the cancer cells bears a marked resemblance
to the cells that normally surrounds the healthy, developing embryo, called
the trophoblast.
When an egg is fertilized, it begins to divide, forming a ball of cells.
Before it even leaves the fallopian tube, it grows an external layer of
these trophoblastic cells. It is this trophoblast, not actual the human-to-be,
that attaches onto and aggressively eats a hole in the uterus. It then
nourishes the embryo from a blood pool it creates. (`Trophoblast' itself
means `nourishing germ'.) This trophoblast burrows deeply and implants
the embryo beneath the womb's surface. It eventually becomes the chorionic
villi [see illust.], the fetus's half of the placenta.
The behavior of this tissue is so aggressive and relentless that one
scientist has humorously but accruaely referred to this phase of pregnancy
as the "invasion of the trophoblasts" (Cell 71:355, 1992).
Trophoblast, said Beard, is not only profoundly different, but in many
ways the opposite of normal mammalian cell development. While a normal
cell is a good neighbor, the trophoblast is born to be wild. It is primitive,
corrosive, and invasive. Sound familiar? Of course: these are the very
characteristics of cancer.
One of the mysteries of biology is how and why the embryo survive an
immune system that, by all accounts, should kill it on contact as just
another invading foreigner? Nature has obviously provided that this trophoblast
is able to turn off an otherwise- vigilant immune system, displaying a
sign (`antigen') that says `Baby On Board' to the immune system. In his
article "The Phylogeny of Oncology" (Mol. Biother., 2:137-144, 1990),
Lentz points out that "pregnancy and cancer are the only two biologic
conditions in which antigenic tissue is tolerated by a seemingly intact
immune system."
He concludes his essay with these remarkable words: "It is recognized
that trophoblastic tissue has all the characteristics of a true cancer;
it is deeply invasive, it is highly anaplastic in morphology [i.e., lacks
normal shape], it has a high mitotic index [i.e., frequently divides],
and it produces oncofetal antigens [i.e., shows `Baby On Board']...in
every respect, [it] behaves as a true cancer."
Cancer cleverly follows trophoblast's example, using nature's one big
exception to the rule, like a burglar who first turns off a burglar alarm,
before he robs the house.Without the wildness of trophoblast, and its
devious mechanisms, none of us would even be reading this. Cancer, said
Beard in a provocative insight, is simply trophoblast in the wrong place
at the wrong time, triggered into malignant life by what we would call
hormones and carcinogens.
Beard noticed that in various species trophoblast is stopped in its
forward march when the embryo begins producing pancreatic enzymes. In
humans, he claimed, this occurred during the seventh week of pregnancy.At
that fateful juncture, he said, trophoblast began to lose its aggressiveness.
But if such enzyme production failed, and inhibition did not occur, the
result was the most malignant form of cancer, choriocarcinoma. Beard suggested,
therefore, that the use of pancreatic enzymes be attempted in the treatment
of advanced cancer, since the destruction of the aberrant proteins of
cancer appeared to him to be an unsuspected role of digestive enzymes.
In March, 1909, he persuaded his friend Captain F. W. Lambelle, MD to
treat an ex-drummer of the West Yorkshire Regiment, who had a metastatic
sarcoma of the left upper jaw. Lambelle gave this man 120 injections of
pancreatic enzymes. By the next year, the ex-drummer had completely sloughed
off the cancer and in the following year, when Beard wrote The Enzyme
Treatment of Cancer and Its Scientific Basis (London: Chatto & Windus,
1911; out of print) the patient was still cancer-free. Had the answer
to cancer truly been found?
Some surgeons ridiculously countered that sarcomas were not really cancers!
However, more serious challenges arose when others were unable to reproduce
Beard's work—"countless failures," as Beard admits. Beard responded
plausibly that commercially available enzymes were generally inactive,
and that doses were commonly too weak or too small. But given the conservatism
of the medical profession, and a growing enthusiasm for radiotherapy,
it is not surprising that Beard's ideas fell into total disuse. He died
in obscurity in 1924.
In 1942, these ideas were rediscovered by Ernst T. Krebs, Jr. and his
colleagues. In July, 1950, they published an article in the Medical Record
on "The Unitarian or Trophoblastic Thesis of Cancer." Krebs continues
as director of the John Beard Memorial Foundation of San Francisco. His
oft-stated belief is that "cancer is trophoblast in spatial and temporal
anomaly, hybridized with, and vascularized by, hostal or somatic cells
and in irreversible and fiercely malignant antithesis to such" (Townsend
Letter for Doctors, Feb.-March, 1993, p. 175).
Krebs is also co-discover of Laetrile, and so the fate of the trophoblastic
theory became intertwined with the trials and tribulations of that apricot
kernel-derived chemical. A final blow seemed to come in 1990, when a prominent
laetrilist, Robert Bradford, announced that modern research had undermined
the trophoblastic thesis. "Say goodbye to an old friend," he wrote in
The Choice.In this article, Bradford raised many technical objections
to the Beardian thesis. And indeed many questions need to be answered
before this theory can be accepted as fact. What is remarkable, however,
is how two scientists have now independently proclaimed their belief in
an updated version of that theory, arriving at their conclusions without
studying Beard's seminal work.
