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Scientists Identify Stem Cells As Hidden Cause of Cancer, Part 2

As I discussed last week, Michigan scientists recently announced that a malignant form of stem cells may be responsible for the development of breast cancer. According to a University of Michigan press release, their new understanding is "a paradigm shift in cancer research," and the University has promised to raise $12 million to investigate this concept.

But actually this research has very old antecedents. In 1902, Prof. John Beard of Edinburgh first proposed "germ cells" as the ultimate cause of cancer. These germ cells, he said, were in a sense capable of giving rise to other types of differentiated cells found in an organism. In 1998, mainstream scientists made a huge leap in understanding cancer when they discovered (and patented) embryonic stem cells (ESC). They did not reference Beard in their paper, but they used the term "totipotent" that had often been applied to describe germ cells, meaning that they were capable of developing into any other tissue.

As in the recent Michigan finding, Beard described these aberrant germ cells as a tiny minority of cells with enormous power that are present in a larger mass of reactive tissue. He actually saw these cells in fishes and reptiles and then speculated on their presence in human tissue as well. From their presumed presence in malignant tissue, Beard came to the conclusion that cancer was in essence a single disease which had many manifestations. (A comparable phenomenon would be syphilis, which can manifest itself so differently in so many different organs that it has been called the "great impostor.") From this point of view, the many and varied characteristics of each kind of cancer are due to the interaction of truly malignant cells with neighboring, normal cells and the reaction of surrounding tissues. This takes place under the influence of hormones and cytokines within the microenvironment of each particular organ or tissue. But, according to Beard's theory, the fundamental origin is almost always the same, i.e., it is trophoblastic in nature.

Pictured Above: A diagram of the development of stem cells

Beard said that the first step on the road to cancer occurred when germ cells differentiated into trophoblasts and somatic cells. When that happens in the course of embryo formation, it is necessary and normal. However, when such a process occurs outside the course of pregnancy, the result is what we call cancer.

There are many points of similarity or identity between trophoblasts and cancer cells. As I discussed in last week's newsletter, it has been found that the truly dangerous and malignant portions of breast tumors have a unique configuration of surface markers: all express a protein marker called CD44, in addition to having either very low levels, or no levels, of another marker called CD24. But in a 1996 article, Israeli scientists demonstrated that CD44 surface markers are also found on trophoblasts. "In this study we found human trophoblasts, for the first time, to express CD44," Dr. Ran Goshen and his colleagues at the Hebrew University in Jerusalem wrote. "Intermediate trophoblasts of the first and second trimester exhibited the standard form of CD44...." So here is another important confirmation of the trophoblast-cancer link.

Looked at from a Beardian perspective this uniformity is not surprising. Nor is the fact that the same markers are found in cancers as disparate as leukemia and breast cancer. One can predict that they will now be found in many other cancer types as well. It also helped confirm Beard's theory when modern scientists announced that human embryonic stem cells (ESCs) produce and release the hCG hormone.

As I wrote last year on the 100th anniversary of Beard's discovery, the relationship between Beard's germ cells and contemporary totipotent stem cells deserves further study. More and more, trophoblast and cancer look like two names for the same general phenomenon. Further research will hopefully lead to a revived interest in Beard's contribution, and an incorporation of his powerful ideas into contemporary stem cell research.

Implications for Treatment

It is understandable that U-M scientists, excited by their important findings, would think that an answer to cancer lies in their newly isolated cancer stem cells. The University of Michigan has in fact filed a patent on Dr. Clarke's discovery of stem cells in cancer and Dr. Clarke and his colleagues have also formed a new company called Cancer Stem Cell Genomics (CSCG) to develop and test new therapies to destroy or disable these cells. Dr. Wicha has said that "now that we can actually identify [the cancerous stem cells], we can start developing treatments to specifically target and hopefully eliminate them."

Naturally, I wish them good luck. However, judging from Beard's pioneering work, they may find that there is a missing link in this process. In Beardian terms, the stem cell is like a loaded gun. In and of itself it is not the cause of cancer. What 'pulls the trigger' is the differentiation of the tumor's stem cell into a malignant component of cells that are trophoblast-like in their nature.

In February 1905, Beard theorized that "the secretion of that important digestive gland, the pancreas," could be employed as a natural form of cancer treatment. The first evidence that injections of the pancreatic proteolytic enzyme trypsin did indeed kill cancer cells was published within the following year. In later years, Beard also turned his attention to the carbohydrate digesting enzyme, amylase (which is sometimes overlooked in contemporary enzyme preparations).

In fact, the therapeutic use of pancreatic enzymes flows effortlessly from recognition of cancer as a trophoblast. Beard's reasoning on the subject was as follows. The trophoblast itself is extremely dangerous when it occurs outside the normal placenta. If it overgrows, it forms a kind of cancer called 'choriocarcinoma.' This is a dreaded malignant pregnancy, which (before the introduction of chemotherapy) resulted in the rapid death of both the mother and her fetus. However, Beard said, on the 56th day of gestation the human trophoblast normally stops its progression. What happens on that fateful day? The fetal pancreas starts producing juices containing pancreatic enzymes. Since the fetus doesn't have, or need, a functioning digestive system that early in its development (since all nutrients come to it from the mother, through the umbilical cord) these enzymes have to have another function. Beard's conclusion was that pancreatic enzymes, in addition to their obvious digestive role, also play a role in "digesting" trophoblasts or (later in life) trophoblast-like cancer cells.

In 1911, Beard published his only book, The Enzyme Treatment of Cancer and Its Scientific Basis. His ideas generated considerable attention at the time. The Encyclopedia Britannica (1911) noted:

"Then we have Beard's 'germ-cell' hypothesis, in which he holds that many of the germ-cells in the growing embryo fail to reach their proper position--the generative areas--and settle down and become quiescent in some somatic tissue of the embryo. They may at some later date become active in some way, and so give rise to a cellular proliferation that may imitate the structure in which they grow, so giving rise to new growths."

Beard based his claims not just on laboratory work but on several cases of apparent remission that followed treatment with enzymes. In March 1909, his friend, Captain F. W. Lambelle, MD, then at the Military Hospital in York, treated an ex-drummer of the West Yorkshire Regiment who had a metastatic sarcoma of the left upper jaw. Lambelle gave the man 120 injections of pancreatic enzymes. By the following year, the ex-drummer had completely sloughed off the cancer and remained cancer-free for at least two years. Another cancer - this time a case of breast cancer - was also successfully treated.

However, other physicians were unable to consistently reproduce this work. There were "countless failures," as Beard himself admitted. He believed, with some justification, that commercially available enzymes were of variable quality, and that inadequate doses had often been administered to patients. Due to the lack of reproducible results, interest in his ideas fell away. He died in 1924, a disappointed man. A lifelong bachelor, he left no progeny nor any personal information beyond what can be gleaned from his scientific writings.

Beard's ideas fell out of fashion for many years. But they are no longer entirely strange to the medical establishment. Because of the pioneering work of Nicholas J. Gonzalez, MD, of New York City, the National Institutes of Health (NIH) has invested $1.4 million in an ongoing clinical trial at Columbia University of an enzyme-based regimen as a treatment for advanced pancreatic cancer. One senses that some of the brightest minds in both academic and integrative medicine are converging on a point that will offer tremendous insight and hope in the struggle against cancer.

--Ralph W. Moss, Ph.D.

Acknowledgement: My thanks to Dr. Nicholas Gonzalez, Dr. Michael Clarke and Robert Scott Cathey for helpful comments. Needless to say, any remaining errors are entirely my own.

Note: If you want to learn more about this topic, in 1998, I spoke at a session of the Comprehensive Cancer Care conference with Drs. Acevedo, Regelson and Gonzalez. This session is available online at:

http://www.cmbm.org/conferences/ccc98/transcripts/205.html

For more articles on the 100th anniversary of Beard's theory, see:

http://www.cancerdecisions.com/062602_page.html

and

http://www.cancerdecisions.com/070202.html

If you are interested in learning about the best currently available conventional and alternative treatments for a particular kind of cancer, please consider buying one of our detailed Moss Reports. Call us at 1-800-980-1234 or visit our website at www.cancerdecisions.com.

References:

Al-Hajj M, et al. From the cover: prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8.

University newsletter: http://www.med.umich.edu/opm/newspage/2003/tumorsc.htm

Steinberg D. Stem cell discoveries stir debate. The Scientist 2000;14:1. Accessed at:
http://www.the-scientist.com/yr2000/nov/steinberg_p1_001113.html.

Thomson JL, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-7.

Goshen R, et al. Hyaluronan, CD44 and its variant exons in human trophoblast invasion and placental angiogenesis. Mol Hum Reprod. 1996;2:685-91.

U.S. Patent No. 5,843,780, "Primate embryonic stem cells"; accessible at www.uspto.gov.

Beard J. Embryological aspects and etiology of carcinoma. Lancet 1902;1:1758.

Beard J. The Enzyme Treatment of Cancer. London: Chatto & Windus, 1911.

Acevedo HF, et al. Detection of membrane-associated human chorionic gonadotropin and its subunits on human cultured cancer cells of the nervous system. Cancer Detect Prev. 1997;21(4):295-303.

Acevedo HF and Hartsock RJ. Metastatic phenotype correlates with high expression of membrane-associated complete beta-human chorionic gonadotropin in vivo. Cancer. 1996 Dec 1;78(11):2388-99.

Acevedo HF, et al. Human chorionic gonadotropin-beta subunit gene expression in cultured human fetal and cancer cells of different types and origins. Cancer. 1995 Oct 15;76(8):1467-75.

Regelson W. Have we found the "definitive cancer biomarker"? The diagnostic and therapeutic implications of human chorionic gonadotropin-beta expression as a key to malignancy. Cancer. 1995;76:1299-301.

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