“Lyme On the Brain” continued…
Lecture Notes of Tom Grier: Tom Grier (Microbiologist from Minnesota) spoke at Lac Court Oreilles Convention Center in Hayward, WI. Tom’s life work is to do further research and bring awareness of this illness to everyone. For more info about Tom and his work checkout http://www.mibdec.com
We have talked about how the Lyme spirochete attaches to the endothelial cells in blood vessels, and creates “LEAKY” blood vessels. Due to the spirochete’s exceptional motility, this allows the bacteria to enter virtually any tissue in the human body.
The big questions are: Where is it going? Why does it want to go to specific places? What happens when it gets to places where it can hide and survive?
Bacteria don’t have brains, but they do have millions of years of evolution that improved their overall survival through shear trial and error. The bacteria wants to survive.
For good or bad Borrelia bacteria have made their homes in ticks and mammals. How has evolution affected their genetics in order to enhance their own survival in ticks and mammals?
Let’s look at Borrelia bacteria from the bacterium’s point of view.
All known species of Borrelia bacteria that cause Relapsing Fever and Lyme Disease enter the blood of humans either by way of an insect bite such as from an infected tick, head-lice, or through infected blood contact.
Relapsing Fever caused by Borrelia recurrentis enters the blood stream through open bleeding capillaries on the head caused by the host scratching at lice and themselves until they are bloody, and then accidentally crushing the head-louse allowing the bacteria direct entry into the blood stream.
Dr. Joseph Dutton was infected with Borrelia duttonii when he was performing an autopsy on an African native who died very quickly of neuroborreliosis-encephalitis after contracting Relapsing Fever through the bite of the moubatta tick.
Unfortunately Dr. Dutton cut himself during this field autopsy, was also infected, and died of encephalitis within two weeks of initial infection.
Below is an excerpt from Dr. Willy Burgdorfer’s lecture on the history of spirochetes related to Lyme disease.
Take special note about the disappearance of classical formed spiral spirochetes in favor of granular-cysts, and also the ability of Borrelia to invade epithelial cells and appear to have disappeared.
This is a history and research that we cannot ignore and cannot afford to forget.
If we had looked at this evidence in 1982, we would have understood the paradoxes we were seeing and incorrectly dismissing as artifacts, in our diagnosis, treatment, and relapses of Lyme patients.
At the turn of the century, 1903 through 1905, the British physicians Dutton (Joseph Everett) and Todd (John Lancelot) working in the Congo, found that the disease referred to as “human tick disease” by David Livingston as early as 1857, was caused by a spirochete transmitted by the African soft-shelled or argasid tick, Orhithodoros moubata (Fig. 3).
Both Dutton and Todd contracted the disease.
Dutton, a pathologist, infected himself accidentally during a post mortem and died.
He is remembered by having had named the East African relapsing fever spirochete Borrelia duttonii.
Also playing an important role in relapsing fever research was the German microbiologist Robert Koch. At the end of 1904, he was called to East Africa to investigate the widely distributed East Coast Fever in cattle.
He soon learned that most Europeans traveling into the interior regions had been suffering of recurrent fever first thought to be malaria.
Although Koch was not aware of the British findings in the Congo and Uganda, he confirmed the vector role of the Orhithodoros moubata.
He was the first to demonstrate that spirochetes were transmitted via eggs (transovarial transmission) to the progeny of infected female ticks.
Ever since it was demonstrated that the body louse (Pediculus humanus humanus) and the African O moubatawere the vectors of the relapsing fever spirochetes known today as Borrelia recurrentis and B duttonii, respectively, intense studies have been carried out on the development of these microorganisms in their vectors, and on the mode of transmission to humans.
Thus, in 1912, the French worker Charles Nicolle and coworkers studied the behavior of B recurrentisin lice and noted that the spirochetes had disappeared from the midgut 24 hours after they had been ingested; they were no longer detectable until days 6 to 8 when they suddenly reappeared in the hemolymph.
A similar “negative phase” had previously been reported for B duttonii in O moubata by:
- Dutton and Todd (1905-1907),
- Leishman and other investigators (1907-1920),
- Fantham (1911-1915),
- Hindle (1911),
- later also by Hatt (1929) and
- Nicolle and associates (1930).
According to these investigators, ingested spirochetes invade the gut epithelium where they lose motility and after 3 to 4 days develop into cysts (blebs, vesicles) that contain granules or chromatin bodies (Fig. 4).
Dutton and Todd postulated that these spherules are formed by protuberance of the spirochetes periplasmic membranes;they may occur at any point along the spirochete.
At some time during their development, these spherules or cysts were said to burst and release their granules.
By the 10th day after infectious feeding, Dutton and Todd no longer found morphologically typical spirochetes, but instead large numbers of granules from which eventually new spirochetes developed provided the ticks were maintained at temperatures above 25° C.
Hindle, in 1911, reported similar observations. In infected ticks held at 21° C, the spirochetes had disappeared from the midgut by the 10th day after infectious feeding.
They could no longer be detected either in the gut or in the tissues.
However, triturates of such ticks injected into mice regularly proved infective, and an increase in temperature to 35° C resulted in the reappearance of morphologically typical spirochetes.
This “granulation theory” — as it was referred to — received a significant boost in 1950 when Edward Hampp of the National Institute of Dental Research in Bethesdashowed by stained smears, darkfield and electron microscopy that oral treponemes and Borrelia vincenti in cultures produce blebs and granules that were considered “germinative units.”
His hypothesis was supported by the observation that 31- month old cultures containing only granules invariably resulted in typical spirochetes upon transfer to fresh medium.
DeLamater and coworkers also reported similar observations from the University of Pennsylvania Medical School.
They provided evidence for the occurrence of a complex life cycle in the pathogenic and nonpathogenic strains of Treponema pallidum.
Accordingly, these spirochetes multiply by:
(1) transverse or binary fission, and
(2) by producing gemmae (cysts in which a single or more granules appeared to be the primordia of daughter spirochetes).
Once the Borrelia Lyme bacteria enter the blood stream of a human, it is immediately susceptible to attack.
An immediate cellular response of neutrophils and macrophage will try and digest the bacteria, and also present markers for the bacteria to lymphocytes that will over the course of several weeks begin to turn out killer T-cells and B-cells that produce specific antibodies.
The first mechanism to survive is to leave the blood stream!
Borrelia can do this by either entering the blood vessel cells called endothelial cells, or transiting the blood-vessel through gaps it creates, and entering other tissues.
If the bacteria do this quickly enough, not enough bacteria will be present to cause an immune response. In other words, it tricks the immune system into thinking that there is no active persistent infection.
If the infection load in the blood is too low, the immune response is muted. But the bacteria can persist in low numbers in other tissues.
Often the first tissues the bacteria find themselves in; is back in the skin usually at the tick-bite-site.
The cellular response to attack the bacteria that is literally swimming through the skin cells, causes the redness, and the appearance of the rash.
Over time parts of the rash fade as the immune response lessens as the bacteria move away from ground-zero.
Another place Borrelia burgdorferi can hide is in the skin. We have seen in culture that fibroblast skin cells can safely harbor the bacteria, and prevent powerful drugs like IV ceftriaxone at high concentrations to have almost no lethal effect on the sequestered bacteria.
If we can’t kill the bacteria in in-vitro skin studies, why would we think we have any better luck in a living human when there are even better places to hide?
Georgilis K, Peacocke M, and Klempner MS. Fibroblasts protect the Lyme Disease spirochete, Borrelia burgdorferi from ceftriaxone in vitro. J. Infect Dis. 1992;166:440-444
It isn’t what we don’t know about Lyme disease that is causing patients to suffer. It is what we have known and chosen to ignore that is slowly killing patients by diminishing their quality of life until they have nothing left to fight with.
Once the bacteria enter the blood stream, with every beat of the heart the bacteria are dispersed throughout the body. These motile leech-like creatures use their ability to swim and their ability to attach to cells to their advantage to survive.
Dr. Russell Johnson PhD University of MN, reported at a Lyme research conference workshop I attended in Bloomington, Minnesota, that hamsters infected with Borrelia had live bacteria within their tendons within 4 days of experimental tick bite, and the bacteria was detectable in the brain of the rodents within a week.
But because this research was for a drug company with an antibiotic seeking an indication for use against Lyme disease, and the antibiotic failed to eliminate the infection from the hamsters unless dosed four times a day at twice the normal dose instead of just once a day dosing as the drug company desired; the research was never published and the drug for other reasons was later removed from the American market altogether.
How much other research useful to suffering Lyme patients has been lost because of the pursuit of patents, indications, and market share?
I can tell you after attending over 20 International Lyme conferences, that much of the best research information is never fully published.
Take for example the Nantucket Island Lyme Patient Treatment Study that lasted over five years. Although it was funded by public monies; only those who attended a research symposia saw the raw data about antibiotic failures and the overall failure and patient relapse rate of over 50 % after five years of follow-up.
Yet the conclusion of the published study said there were no long-term consequences that were serious: Serious to whom? Do you wonder what they will leave out in ten years?
So we know the bacteria can evade the immune system and sequester itself, but over time where does it want to be?
One suspected food source is N-Acetyl-Glucosamine, a component of connective tissue.
Coincidentally we see many joint and connective tissue problems in Lyme patients, and we have found the live Lyme bacteria within human patient’s ligaments despite aggressive antibiotic therapy.
Haupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schonnherr U, Kalden JR and Burmester GR: Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme Borreliosis. Arthritis and Rheum 1993;36:1621-1626
Schmidli J, Hunzicker T, Moesli P, et al, Cultivation of Bb from joint fluid three months after treatment of facial palsy due to Lyme Borreliosis. J Infect Dis 1988;158:905-906
Once the Lyme spirochete has found a food source like inside a tendon or joint, it must also be protected. Since the tendons and connective tissue are poorly oxygenated and few immune cells circulate there, they have a safe haven.
Occasionally we see heart complications, and arrhythmia issues. This is because the bacteria is also attracted to nerve cells and related tissues.
Within the heart there is a web-like network of nerve cells called the purkinje fibers. These fibers regulate the controlled contractions of the heart by a coordinated conduction system that keeps the contractions even and regular.
Between each of these nerve fibers is a rich source of N-Acetyl-Glucosamine, and coincidentally on tissue biopsy and stain, we see the spirochete lined up parallel to the nerves and buried within this food source.
Sometimes this leads to myocarditis, myocardiopathy, and arrhythmias like atrial fibrillation, tachycardia, bradycardia, and 2nd degree-heart-block.
In our Duluth, Minnesota, Lyme disease Support group, we had a Lyme patient who was on the waiting list for a heart transplant.
After six months of oral amoxicillin for Lyme, his cardiomyopathy improved to the point where he was no longer disabled, no longer needed a heart transplant, and became a fish farmer on the Iron Range.
His $300 of amoxicillin saved him $100,000 and a life of always being on anti-immune, rejection drugs.
Goodman JL, Sonnesyn SW, Holmer S, Kubo S, Johnson RC.: Seroprevelence of Borrelia burgdorferi in patients with severe heart failure, evaluated for cardiac transplantation at the University of MN. Abstract # 49, presented at the Fifth International Symposia on Scientific Research on Lyme Borreliosis, Arlington, VA, 1992 *
13 % of patients awaiting heart transplant tested positive by ELISA test.
Now we saw earlier just how poor this test was at detecting Lyme disease and that false positives were low. Yet the prevailing explanation from university researchers for these positive patients was “false-positives”.
I guess I would believe that if we didn’t currently have another Lyme patient awaiting a heart transplant; he is also part of our 3-year documentary on Lyme disease in Minnesota/Wisconsin, and has requested an extensive autopsy to look for Lyme if he dies.
The hard truth is that patients are willing to die to find the truth, but our health care system refuses to do any autopsy studies on Lyme disease? Why? It is the gold standard.
Autopsy is the answer to all our questions. Not to do a national multi-center autopsy study is a way of saying “We don’t really want to know the truth.”
The joints, heart, and skin are good places to hide, but this bacterium is seeking a better place to survive.
We have seen that over time untreated Lyme rashes go away all by themselves. This is because the immune system has suppressed or eliminated the bacteria, or exposure to severe heat like saunas has killed the heat labile organism.
(Borrelia cannot tolerate temperatures above 108 F for more than twenty minutes.
But to get our core temperature and brain to that temperature would kill us, so all we can do is use heat as an adjunct to kill the bacteria in our skin and help deliver more antibiotic deeper because of vasodilatation of blood vessels.
This was done to treat Syphilis, and when penicillin came out commercially in the mid 1940s, hot springs across the nation went out of business. ) See Dr. Bundeson in the book by: DeKruif, Paul: Life among the Doctors. Pp140-168
This place where the Lyme bacteria seeks is ideal. The human brain is so selective to what it allows in that it even keeps out white blood cells. Without white blood cells the bacteria has no enemies.
The bacteria swims through the blood-brain-barrier blood vessels early in infection, and then when the barrier reseals itself, the bacteria is not only safe from immune assault, but also antibiotics have trouble getting into the brain.
Some antibiotics like IV-ceftriaxone and other cephalosporin’s get into the brain but they don’t penetrate inside brain cells. Why is this important?
Well it turns out that Borrelia burgdorferi can penetrate into brain cells quickly and easily, and once they do; they can sit quietly in a non-metabolic dormant state. No amount of antibiotic can kill a dormant spirochete.
Now put it inside a cell, inside a brain behind a protective barrier, now keep out the immune system, and make sure the temperature stays nice and low like the brain prefers.
Now you have an incubator for long-term bacterial survival and eventual neurological problems that may take years to develop.
If what I am telling you is true, then surely we have seen spirochetes associated with neurological disease before? Yes, Syphilis dementia and paresis is well documented, but what else are we missing?
MS and Spirochetes
In every Lyme disease support group in this country (and I have visited dozens), there have always been at least one multiple sclerosis, MS, patient who turned out to have Lyme disease, and was recovering on antibiotics.
But if this is true why is there is no documented connection between spirochetes and M.S.?
As it turns out there are more than 50 such MS-spirochete references prior to World War II and going back to as far as 1911, and published in such prestigious journals as the Lancet.
- 1911 Buzzard Spirochetes in MS Lancet
- 1913 Bullock MS Agent in Rabbits Lancet
- 1917 Steiner Spirochetes The Cause of MS Med Kiln
- 1918 Simmering Spirochetes in MS by Darkfield Micro
1918 Steiner G. Guinea Pig Inoculation with MS infectious agent from Human
- 1919 Steiner MS Agent Inoculation into Monkeys
- 1921 Gye F. MS Agent In Rabbits Brain 14:213
- 1922 Kaberlah MS Agent In Rabbits Deutch Med Works
- 1922 Sicard MS Spirochetes in Animal Model Rev Neurol
- 1922 Stepanopoulo Spirochetes in the CSF of MS Patients
- 1923 Shhlossman MS Agent in Animal Model Rev Neuro
1924 Blacklock MS Agent in Animals J. of Path and Bac
- 1927 Wilson The Rat as A Carrier of MS British Med Journal
- 1927 Steiner G Understanding the Pathogenesis of MS
1928 Steiner Spirochetes in the Human Brain of MS Patients
1933 Simons Spirochetes in the CSF of MS Patients
1939 Hassin Spirochete-like formations in MS
- 1948 Adams Spirochetes within the Ventricle Fluid of Monkeys Inoculated from Human MS
- 1952 Steiner Acute Plaques in MS and The Pathogenic Role of Spirochetes as the Etiological Factor Journal of Neuropathology and Exp Med 11: No 4:343 1952
- 1954 Steiner Morphology of Spirochaeta Myelophthora (Myelin Loving) In MS Journal of Neuropathology and Exp Neurol 11:4 343 1954
- 1957 Ichelson R. Cultivation of Spirochetes from Spinal Fluids of MS Cases with Negative Controls Procl. Soc. Exp. Biol Med 70:411 1957
If you follow the European Medical Literature concerning Multiple Sclerosis from 1911 to 1939, you find that in France, Germany and England; there were independent researchers all observing similar things and coming to similar conclusions:
1) Spirochetes are often found in conjunction with the lesions in the brains of patients who have died with MS.
2) These spirochetes can be isolated and can infect many mammalian animal models; including: mice, rats, hamsters, guinea pigs, rabbits, dogs, and primates.
3) The spirochetes could be re-isolated from the brains of the infected animals and be inoculated into more un-infected animals and re-isolated from their brains.
Why in the 21st century have spirochetes been ignored as infectious agents of the human brain?
The short answer is that to save time and money we no longer do things old school by which I mean:
- no one does brain autopsies and physically stains or cultures for the bacteria.
- Instead we have gotten lazy and cheap in our research and tried to rely on blood tests and CSF fluid to give us the answers.
- But those tests are wholly inadequate to detect living spirochetes sequestered inside brain cells.
Now this is the important part about detecting spirochetes within human tissues.
First you cannot find spirochetes if you don’t properly stain the tissue for them.
Spirochetes are completely invisible under the microscope without special stains.
In 1911, chemists and microbiologists only had silver stains that stained nucleic acids, and for some reason these stains caused the entire spirochete to turn black and opaque.
(It turns out that Borrelia’s nucleic acid is nearly evenly distributed under its inner membrane like a web of DNA that fits the entire bacterium like a nylon stocking
surrounding the cytoplasm.
In other words the silver stain outlines the shape of the bacterium.)
The trouble with silver stains is that they cannot enter human cells. So for nearly a century it was reported that spirochetes were mostly extracellular and found outside all human cells.
Not only was this a wrong conclusion based on inadequate methods,but the consequences of not recognizing an intracellular infection was and still is dire. Why?
Because intracellular infections can be incurable or at the very least more difficult to treat; there is almost no way to determine an end point where a bacteriological cure has been obtained.
Next is that spirochetes are known to disappear by changing to cyst forms, and also by going intracellular.
So these puzzled researchers that were only seeing classical formed spirochetes in 1 in 20 MS patients, may have been seeing them all along and not realizing what they were seeing. How can we conclude this?
Researchers wanted to see if the infectious agent was still in MS lesions despite no visible spirochetes.
Researchers removed brain tissue at necropsy of human patients and inoculated the tissue into uninfected animals.
In some cases, this caused the infection to occur and show up in the brain of the animals; sometimes the classical-form spiral shaped spirochetes emerged.
All of this meticulous work was done prior to WW II, and completely untainted by today’s politics and special interests; yet this body of work is being wholly ignored.
Here is a lesson from history that we should learn:
During our bicentennial year in Philadelphia in 1976, a new disease emerged. An infectious pulmonary disorder suddenly infected and ravaged many people who attended a hotel where there was an America Legion convention that was being held.
When 180 people got sick; 29 of them despite early and aggressive supportive therapy died; it was clear that this was no ordinary flu or pneumonia.
Because it appeared that the mystery illness might be being passed from person to person; immediately it was given epidemic status and the CDC stepped in.
But they were flabbergasted to say the least. Since they could not see bacteria in the lungs of the victims they assumed it had to be a virus, but all their time consuming virus searching did not yield a single clue.
Desperate to find answers at any cost, tissues especially lung tissues were sent to many scientists. Despite nearly an estimated 500,000 man-hours, the cause of the mystery illness was still unknown. It remained seemingly invisible under the microscope.
It is amazing to me that in the annals of medical history; we do not recognize the role of serendipity and credit people who made a difference. You have to look long and hard to find the real story of solving Legionnaire’s Disease.
To look back, you would think the CDC just walked in and solved it with a faceless team of experts and credit given to a government agency; not the work of an individual workaholic microbiologist poking around hot springs and an expert in soil bacteria.
Dr. Carl Fliermans solved the first part of the puzzle when he discovered that Legionella pneumophila lipids resembled those of the thermophilic bacteria he’d found in the thermal regions of the Yellowstone National Park, and that this bacteria tended to live as biofilm (scum) associated with certain species of algae.
Subsequently, Fliermans began poking around aquatic habitats and found – guess what? – this bacteria was residing in thermal waters discharged from a nuclear reactor at Savannah River Laboratory.
This bacteria was later found to be living in natural hot springs all over the United States and, most importantly, in air-conditioning cooling towers.
Once the bacteria were known, special stains for soil bacteria, and special culturing techniques solved the Legionnaire’s mystery.
What was invisible to hundreds of microbiologists could now be seen because of the right stain and right culture technique that was outside the realm of the CDC’s medical team.