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San Marcos University College of Veterinarian Medicine

Lima, Peru Lectures 8/99

by Harold W. Clark, Ph.D.

Mycoplasma Research Institute, PO Box 640040, Beverly Hills,

FL 34464-0040; E-mail: www.hwcmri@hitter.net

Foundation for Eradication of Rheumatoid Disease

AKA The Arthritis Trust of America

7376 Walker Road, Fairview, TN 37062

www.arthritistrust.org

Harold W. Clark, Ph.D.

Lecture I: Mycoplasmas Properties and

their Role in Autoimmune Diseases

Thank you for inviting me to lecture on Mycoplasma Arthritis

in humans.

Today I will review “Mycoplasmas Properties and their Role

in Autoimmune Diseases,” by Harold W. Clark, PhD

In 1952 when I joined Dr. Thomas McPherson Brown, chief

of medicine at the George Washington Univ. Medical School in

Washington, D.C, as Research Biochemist, the chief of medicine at

the University of Rochester in New York told me that Dr. Brown

has a theory that some atypical microbe was the cause of

Rheumatoid Arthritis that should be treated with antibiotics.

Unknown to me, the year before, 1951, Dr. Brown and staff had just

published and reported at the International Arthritis meeting their

recent findings entitled “A Study of the Antigen-Antibody

Mechanism in Rheumatoid Diseases”. This report emphasized the

antibiotic treatment of rheumatoid diseases based on the suspected

mycoplasma role in the inflammatory immune complex that

should be blocked by immunosuppresing agents.

Because of its potential application the report was widely

publicized in newspapers and magazines. For example the

Associated Press reported “Hope Held out for Cure of Rheumatic

Ills, Washington research team announces New Concept on Causes

and Cures”. At that time except for the veterinarians, very few

doctors knew what a PPLO or mycoplasma was, let alone its role in

human arthritis.

Although Koch and Pasteur had brought bacteria to the

forefront of medicine it was the microbiologists Nocard and Roux

at the Pasteur Institute in 1898 that first isolated a filtrable bacteria

from pneumonic and arthritic cattle. For the next 65 years new

isolates were referred to as Pleuropneumonia-Like Organisms

(PPLO), now known as Mycoplasmas in the broader Mollecutes

family.

The terms PPLO and wall-less bacteria L-forms were used

interchangeably until 1962 when a viral-like agent causing

atypical pneumonia but sensitive to tetracycline and cultured in a

cell-free media was found to be a new human mycoplasma strain

(M. pneumoniae). Because of the increasing number of strains,

PPLO were classified under bacterial Mollecutes with the

mycoplasmatacae family and subspecies mycoplasma and

ureaplasma. Our modern day culture techniques have improved

over the early technique of implanting a cellophane bag with the

specimen in a rabbit’s abdomen. The difficulties in isolating

mycoplasmas from inflamed tissues still remains.

Since their first isolation, a major impediment to mycoplasma

research and laboratory diagnosis of infection has been the

difficulty of isolating mycoplasmas from the host tissues. To

overcome this problem complex cell-free media are used for both

isolation and cultivation. The media is usually based on beef heart

infusion, peptone digest, yeast extract, serum and various

supplements. The continued use of these complex undefined

media components has limited the precise definition of

mycoplasma’s metabolic pathways, genetic analysis, preparation

of mycoplasma antigens free of media components and specific

monoclonal antiserum free of endogenous antibodies. The ability

to detect and identify mycoplasmas in tissues using the genetic

Polymerase Chain Reaction (PCR) technique should be measured

in relation to the host’s immunologic and other responses to an

infection. In addition there is some concern about the adaptation of

new mycoplasma isolates being changed when grown in artificial

media and subjected to viruses.

The first question we should ask and define is “What are

Mycoplasmas?” And what are their connections with human

arthritis especially the chronic rheumatic diseases of unknown

origin. If mycoplasmas are now known to cause arthritis in animals

as well as acute and chronic disease in human lungs and the

genitourinary tract their location in human joints could also be the

irritant causing inflammation. Thus we have mixed tissue arthritis

with a combination of symptoms. Mixed arthritis is further

complicated by adding another vague term “Rheumatoid

Arthritis” (RA). According to the U.S. Arthritis Foundation, the

whole group of Rheumatic Diseases now constitutes 171 types of

arthritis with associated diagnoses and mixtures of symptoms.

These include mycoplasma arthritis, connective tissue diseases,

and mixed connective tissue diseases. RA was initially called

Chronic Infectious Arthritis, when it was first thought to be caused

by some atypical viral-like agent and is now referred to as

Autoimmune disease, Immune Complex disorders, and Collagen

Vascular disorders. The diagnostic terminology is more confusing

when based on the symptoms, the tissue targeted, the disease

mechanisms, and the microbial causes. This terminology includes

septic, reactive or infectious, bacterial, viral, Lyme, and

mycoplasma arthritis in humans. The mixed symptoms caused by

mycoplasmas are not the same as caused by bacteria and viruses.

The different responses are attributed to mycoplasma’s different

physical, chemical and host related properties.

What is Mycoplasma Arthritis?

The common symptom in most Rheumatic Diseases is

inflammation as anatomically described by synovitis, bursitis,

carditis, neuritis, or nephritis, etc. Many different causes of

inflammation have been suggested and pursued. Upon further

study and review, researchers may find that a common microbe,

such as Mycoplasmas can cause various host responses or