Cancer bacteria

Overview
Cancer bacteria refers to bacteria (not viruses) known or suspected to cause cancer. Some of these may in fact be opportunists: bacteria present in the environment that colonize a host made vulnerable by cancer. As such, cancer would be the cause, and bacterial infections the effect, rather than the other way around.

In 1890, German bacteriologist Robert Koch defined four requirements to prove that a given organism causes a given disease. These requirements, known as Koch's postulates, guide research into the bacterial cause of many diseases, including cancer, and establish a gold standard of evidence consistent with "proof".

Known to cause cancer
Helicobacter pylori colonizes the human stomach and duodenum. In some cases it may cause stomach cancer and MALT lymphoma. Animal models have demonstrated Koch's third and fourth postulates for the role of Helicobacter pylori in the causation of stomach cancer.

Suspected to cause cancer
Mycoplasma has been implicated in the formation of cancer. Specific reports include:
 * Mycoplasma can “induce malignant transformation of host mammalian cells” by means of "aberrant expression of oncogenes and tumor repressors".
 * A "Mycoplasma hyorhinis-encoded protein known as p37…..(could) infect humans and may facilitate tumor invasiveness".
 * A “significantly high existence of Mycoplasma sp. DNA" has been reported "in the tissues of patients with conventional (renal cell carcinoma)" as opposed to normal controls.
 * "Mycoplasma infection can be detected in many tumor tissues; continuous infection of mycoplasma can lead to transformation of mammalian cells, up-regulating expression of oncogenes, and some biologic changes of tumor cells, suggesting association of Mycoplasma infection with tumorigenesis"

A number of other bacteria have associations with cancer, although their possible role in carcinogenesis is unclear. Salmonella typhi is associated with gallbladder cancer, Streptococcus bovis is associated with colorectal cancer and Chlamydia pneumoniae with lung cancer.

History
In 1890, the Scottish pathologist William Russell reported circumstantial evidence for the bacterial cause of cancer. In 1926, Canadian physician Thomas Glover reported that he could consistently isolate a specific bacterium from the neoplastic tissues of animals and humans. One review summarized Glover's report as follows:


 * "The author reports the isolation of a pleomorphic organism from various types of cancer which can be grown in pure cultures in its several phases. He produced a serum from it which has given remarkable results in a series of 50 reported cases.  This is very important, if true.  We suppose the Cancer Society will give an opinion later on the reliability of the findings."

Glover was asked to continue his work at the Public Health Service (later incorporated into the National Institutes of Health) completing his studies in 1929 and publishing his findings in 1930. He asserted that a vaccine or anti-serum manufactured from his bacterium could be used to treat cancer patients with varying degrees of success. According to historical accounts, scientists from the Public Health Service challenged Glover’s claims and asked him to repeat his research to better establish quality control. Glover refused and opted to continue his research independently; not seeking consensus, Glover's claims and results led to controversy and are today not given serious merit.

In 1931, Cornell University pathologist Elise L’Esperance reported the presence of acid-fast, Tuberculosis-like organisms in Hodgkin's disease, French physician George Mazet implicated a bacterial association with leukemia and also Hodgkin's disease and a number of other physicians or scientists, including the German von Brehmer , the Irish physician W.M. Crofton and EJ Villesquez of France all reported similar cancer bacteria associations. In one case, an Italian scientist named Clara Fonti reportedly inoculated herself in the chest wall with a metastasizing mammary carcinoma and claimed to note neoplastic changes in her own tissues.

In some cases, claims were made that anti-sera derived from cancer associated bacteria could be used therapeutically. In 1953, for example, the results of an anti-bacterial vaccine trial involving 100 patients said to be diagnosed with different stages and types of cancer was reported by Dr. John E. White at the 6th International Congress of Microbiology in Rome, Italy. White said there were a number of favorable responses, but critics noted that the trial was not blinded, supervised, or monitored by any independent mainstream cancer agency, and the actual severity as well as diagnostic authenticity of the cancers-in-question not verifiable.

In 1950, a Newark based physician named Virginia Livingston published a paper claiming that a specific Mycobacterium was associated with neoplasia. Livingston believed that this organism was intermittently acid-fast, highly pleomorphic, and taxonomically related to the leprae and tuberculin bacilli. She, along with several colleagues including microbiologist Eleanor-Alexander Jackson, continued research throughout the 1950’s and eventually proposed a name for the bacterium, calling it Progenitor cryptocides. Livingston also proposed a treatment protocol based on anti-microbial vaccines similar in concept to Glover's which she reported on in a 1965 publication.

Other investigators were not sure of the exact classification of cancer bacteria, and had claimed to find different taxonomies other than Mycobacteria. For example, I.C. Diller, who had reported an increased "number of tumors" occurring in mice "injected with a bacterium" isolated from mice and human cancers, referred to several possible classifications. These included a Corynebacterium "of undetermined species", Staphylococcus epidermidis and an organism related only antigenically to Mycobacteria. She cited the "extreme pleomorphism" and "tendency to stabilize in forms that mimic other bacteria" as reasons for the difficulty in classification.

Beginning in 1963, the National Cancer Institute (NCI) launched its own preliminary investigation of cancer bacteria, and until 1974, conducted several studies which focused primarily on the culturing of cancer bacteria from animal and/or human cancers in an attempt to establish a guilt-by-association relationship between the two. The NCI investigations involved several different species, including Mycoplasma orale, Mycoplasma fermentans, Mycoplasma neurolyticum and Mycoplasma pneumoniae and many of the studies involved examination of leukemic bloods.

The NCI studies produced various results. In one study, researchers concluded there was no statistically relevant oncogenic association between certain Mycoplasma species. In another, investigators concluded there was “an association between Mycoplasma and acute leukemia”. Another NCI paper stated the “importance of (Mycoplasma/cancer) association(s)” because “latent mycoplasma were repeatedly isolated from mice under stress with malignant disease”.

As of October 1986, however, the NCI’s position was that its bacteria investigation failed to reach a definitive conclusion. NCI and other mainstream investigators---while questioning the actual role of cancer bacteria in oncogenesis---believed that such bacteria were common invaders of cancer tissues, acting more as parasites rather than involved in causality. Mycoplasma are known to be notorious contaminants of laboratory cultures and other media. Throughout the 1980's and up to the present time, the NCI has been actively involved in cancer virus research.

In 1974, Livingston reported an association between cancer-related bacteria and human choriogondatropin (HCG), a growth hormone commonly associated with pregnancy. Hernan Acevedo, a Pittsburgh-based scientist, also reported that HCG could be synthesized from cancer-related bacteria. Livingston believed that HCG was a common denominator linking cancer and bacteria, and alleged that cancer tissues utilize HCG for the purpose of avoiding immunosurveillance, basing her ideas on data suggesting the human embryo uses HCG in the same fashion. In a later critique of Livingston’s claims and methods, the NCI argued that "HCG is produced by a variety of bacteria from both cancer patients, and normal tissues".

Acevedo reported in additional studies that “the synthesis and expression of HCG, its subunits, and its fragments, is a common biochemical denominator of cancer, providing the scientific basis for studies of its prevention and/or control by active and/or passive immunization against these sialoglycoproteins”.

In 1990, the NCI published a review of Livingston's theories and said that her methods of classifying the cancer bacterium she referred to as "Progenitor cryptocides" had contained "some remarkable errors". Independent analysis of this organism using DNA-DNA hybridization technology revealed its actual classification as Staphylococcus epidermidis, not a Mycobacterium as Livingston had stated.

According to Dr. Alva Johnson, a professor at the Department of Microbiology and Immunology at the Eastern Virginia Medical School who had independently reviewed the NCI critique, Livingston had not preserved earlier samples of her cultures taken from the blood and tissues of cancer patients in which she claimed Mycobacteria existed and instead routinely screened cancer patients’ urine samples for HCG-positive bacteria assuming these were positive for Mycobacteria. Johnson noted that Livingston’s assumptions reflected “sloppy” science, and adversely affected the protocols needed to build consensus among medical peers.

Livingston died in 1990 and five years later Dr. Shyh-Ching Lo, a researcher with the Armed Forces Institute of Pathology in Washington, D.C., published a paper titled “Mycoplasmas and oncogenesis: persistent infection and multistage malignant transformation”. According to Lo, Mycoplasma fermentans and Mycoplasma penetrans induced malignant cell transformation in cultured mouse embryo cells, C3H/10T1/2 (C3H) after 6 serial passages lasting 1 wk per passage. He further wrote that up until the 11th passage, “malignant changes were reversible if mycoplasmas were eradicated by antibiotic treatment”, but at 18 passages, “irreversible…..transformation” occurred.

Subsequent to Lo’s paper and as of 2007, there were a minimum of 14 published papers in the peer reviewed literature claiming to document an association between various species of Mycoplasma and various animal and human cancers.

Cancer Bacteria as Contaminants
Scientists have long suspected that cancer bacteria may be contaminants which infiltrate tissue cell cultures, or invade cancer tissues after the disease has started, as opposed to being a direct cause of cancer. Research is now under way in an effort to clarify this relationship.

In a recent study, investigators examined deep tissue specimens taken from patients with Oral Squamous Cell Carcinoma. Using rRNA gene sequencing, and addressing the issue of contamination with sterilizing immersion techniques, the investigators noted a “diversity of bacterial taxa...including several putatively novel species.” Some of the bacterial species were “isolated only from either the tumorous or nontumorous tissue” indicating “a degree of restriction.” The investigators said that “Successful surface decontamination of the specimens indicates that the bacteria detected were from within the tissue”.

Rather than finding one taxonomy, the researchers noted a “diversity of bacterial groups” and concluded that the “significance of these bacteria within the tumor warrants further study".

Related chapters

 * Virus cancer link