17 Video: Shortcuts To Learning Immunology

I realize I posted a 14 part mini-series on Immunology not long ago and know that could be a bit much to bite off at once in order to learn more about the immune system.

So I've been spending time looking for shortcuts - ways for readers to quickly get up to speed on some of the terms and processes used when discussing the immune system.

I figure videos usually are the best way to begin learning for many people - so I have been watching them on Youtube to decide what to post here.

Let me just say that as entertaining as some of them are, I wish more of them were factually correct or just had more educational content in them.

I love the idea of using battle scenes from The Lord of the Rings movies as an analogy for the immune system - some creative guy did this, and it was hilarious. But most of it had no mention of the immune system or how it worked, beyond "the good guys are these immune cells, and the orcs are the invading pathogens". And then there was the guy who went so far as to make a 1950's style documentary on angry macrophages, with retro props and a fake ad for Solomon cigarettes... this documentary compared pathogens to invading Communists.

Unique. Original. Points for style. And yet, next to no substance.

What could have been both an entertaining and educational clip ended up an abysmal failure. C'mon guys, you can do better.


Anyway, I found what I hope are some of the better videos on Youtube that you can watch to learn more about the immune system, and the material on the first one will help you advance to the next video. Also, each video reinforces what you've seen in an earlier one - it helps familiarize you with the terms and concepts used.

Let me know if you have any trouble following these. For those of you who are already more advanced students of immunology and have gotten past all of this, I will be posting more intermediate and advanced videos on the immune system later. (Those who have watched these basic and intermediate videos first will be able to move on to the advanced section, which will mention toll-like receptors and interleukins.)

If you are a more advanced student and already understand those, then I would like to encourage you to comment more here and perhaps start your own blog to let people know more about the science of the immune system and infectious diseases like Lyme disease.

Knowing more about the immune system opens the door to understanding research out there done by the IDSA guidelines panel, scientific researchers in microbiology and molecular biology outside of the IDSA panel, the statements LLMDs have made about Lyme disease and its treatment, and claims other Lyme patients have made online.

Okay, without further delay, here are four videos which may prove useful for beginners - each under 10 minutes:

Immunology Overview [Time: 4:42] - overview of basic parts and terms of the immune system

The Immune System [Time: 9:36] - Basic explanation of the immune system and how it works.

Immune System, Part 1 [Time: 7:59] - Barriers and Non-Specific Defenses
Note that this video is accompanied by this easy to view PDF:
http://www.kirkwood.edu/pdf/uploaded/695/immune_and_lymphatic2.pdf

The Immune Response (Garland Science) [Time: 1:43]

That should be good to get you started.

Note that each one has slightly different information about the immune system, but the core material is the same. Being exposed to this information in different ways over time makes it easier to learn.

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12 Watching Train Wrecks

Every so once in a while, while surfing the net looking for other information related to tickborne infections, I come across blog entries about chronic Lyme disease that not only doubt its existence - but are followed by a firehose of troll-magnet comments from which I, in all my gory stupidity, cannot tear my eyes away.

Referring to the above linked blog post written two years ago, I just had to follow the train wreck to its decisive end: thread closing.

At least it wasn't deleted or moved elsewhere.

Seeing it was a reminder of one of the reasons I don't want ad hominem attacks on comments here. Once people go down that path, at that point they're usually talking past each other and writing parallel monologues anyway - trying to see which side can out-shout the other one.

Nobody is listening to each other at that point. It's not a dialog anymore.

I have to give one of the posters in the above thread credit for trying to explain their point of view - Janis, whoever you are, you posted some interesting research there - thank you.

And I give the primary antagonist on our doom-bound journey - Lance - the award for overlooking others' statements and arguing against something that Janis is not arguing about. Go... Lance... or something. Maybe... just go.

I saw both sides of their argument. I did. It was originally easier to read and see both sides, though, and as the ad hominem attacks and snap responses increased, the more I felt my blood pressure rise.

Lance was saying he thought that all the people who claimed they had chronic Lyme disease couldn't possibly have it, but eventually came across in a condescending manner about his point. Janis kept pointing out that you can't tell whether or not someone does, in fact, have chronic Lyme disease or not  - because they can be seronegative and the tests are unreliable. Lance countered back that he wasn't talking about people who have late stage Lyme disease - but all the people who didn't, had no evidence of infection, and yet claimed they had chronic Lyme disease - when it could have been something else. It continued on from there, with pretty much the same material repackaged in so many ways... Mostly increasingly antagonistic ways.

I can't tell you how many times I have read similar blog posts like the above and predictably know what the outcome is going to be before I even get to the first comment. And I know there will be a long list of completely polarized opinions there, and yet I read it anyway.

Alongside this compulsive behavior,  I suppose it's a healthy sign that I am always on the lookout for what I call the voice of reason - if there is any to be found. Comment #206 by the elusive Dutchman seems to be about the closest thing to the voice of reason.

Around it, there is a lot of chaos... Not to say that people aren't right about their opinion and experience within that chaos - it's just that it isn't very constructive because it ends up a shouting match.

About the one good thing about this is that it typically drives traffic to your web site - whoever the blog owner is probably got a lot of hits that day - just like the Chicago Tribune got a lot of hits for their "dubious diagnosis" article back in December.

Okay - maybe two: some readers of that thread have now been exposed to research that they otherwise would not have seen.

How can these exchanges continue otherwise? How do they get so polarized to begin with?

It doesn't help when one party responds to the other's points by number with 1) Lie, 2) Lie, 3) Lie, 4) Lie and distortion, etc. without clearly pointing out what it was they thought was a lie and what evidence they had to back their assertions. And on a bigger note, one of the problems underlying many of the comments is the fact that the term "chronic Lyme disease" as it has been used by the IDSA in recent years has been almost completely useless - and trying to use it in this thread only adds to the chaos.

After I read something like this, I usually shake my head and think, "What an utter waste of time that was." And I surf on to whatever it was I was originally looking for.

However, I can't shake the fact that every time one of these train wrecks lights up my screen that the same kinds of questions come up:

Why can't everyone take a closer look at all the research from all angles?

Why do they almost always end up with some ad hominem attacks?

Why can't more people have a meta discussion to break the contentious thread into something more constructive - such as why does the IDSA have such a useless and mutable definition for "chronic Lyme disease"?

Why not drive a very wide arc around this argument, bypassing it by asking about how patenting proteins in an organism could lead to issues in research?

How about imagining how much basic research would be conducted today if the Bayh-Dole Act hadn't been passed in 1980?

How about the unintended effects of such an Act on patenting, ethics, drug prices, and the increase in applied science projects?

Sure, these questions seem to become increasingly removed from the issue of persistence. But the point is pretty much laid out for all to see in the elusive Dutchman's comment itself:

"All Janis has kept saying is there needs to be a better test and more research. it seems to me that a lot of these patients are pushing for the same thing, more research, more reliable testing, and better treatment."

And that's just it. If people from both sides of this argument could agree on this much - then the rest of the arguments would eventually fade away.

Underlying the above comment, though, one has to look at what the pitfalls are and have been to getting better tests and research so far - and what can be done to change that situation. Because that is the underlying roadblock here, really, and nothing is going to change without it being addressed.

This work by Camp Other is licensed under a Creative Commons
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1 Part 1: The Value Of Anecdotal Evidence

A few people have asked me in email about why anecdotal evidence is not something that the scientific community tends to accept, and one person even went so far as to say it was stupid to ignore the stories that Lyme disease patients share about their experiences and how certain patients respond to different treatments.

After all, anecdotes are based on real life experiences - and it is possible that a treatment does in fact work and someone's personal experience may be the first indication that there is something meaningful happening - either an improvement in symptoms or a step closer to a cure.

Is ancedotal evidence ever acceptable in scientific research and in professional healthcare? Why or why not?

I'd have to say that in general, it's acceptable on two counts:

1) Cases. When anecdotes are documented very carefully, they are called case reports or a case series. These case reports or case series are about individual patients and doctors' experience in treating them, and their treatment is not part of a controlled experiment. But careful documentation over time of patients' treatments, symptom changes, test results, and other findings at least ensures that information is recorded as events and changes unfold and also can demonstrate other variables which may have led to the patients' conditions (preexisting conditions, addition of new medications, insomnia, etc.).

2) As a means for a starting point for future research. If enough case reports or case series are completed that are pointing to a useful treatment or cure, then this can be used to develop and design controlled studies that can ensure that treatment is specifically helping improve certain symptoms or cure patients. Controlled studies help reduce or eliminate variables which may cloud or muddy the issue of what is or isn't changing patients' conditions, which is why they get more weight as a valid scientific approach than anecdote does.

Under both of these conditions, the information would have to be scrupulously maintained and recorded by someone who is reporting honestly about patients' conditions and their treatments.

Now that these two conditions are defined, what other conditions make anecdotal evidence less acceptable to a scientist who is trying to learn the truth about whether or not a treatment is effective in reducing symptoms or curing a condition?

In a way, we can think back to what I wrote about tomatoes in a comment a little while ago.

Two centuries ago, people in North America and parts of Europe did not make tomato sauce. Pizza as we know it was yet to be invented. The reason was because no one would eat tomatoes, as they were members of the nightshade family and it was believed they were poisonous.

Somewhere along the line, someone must have gotten up the nerve to be the first person to eat a tomato and discover after eating it that they weren't dead. From there, perhaps they went on to discover the joy of fresh salads with tomato, tomatoes roasted over an open fire, and other tomato-based dishes before others began slowly adopting the tomato as an edible item.

That first person could be thought of as brave, stupid, or both. In retrospect, though, most people just eat their spaghetti today without much thought about how people got around to eating it. If that person had been wrong, we would all be sitting around here with more fettucini alfredo than we knew what to do with.

But here's the thing:

What if the first person had gotten sick after eating that first tomato, and lived to tell about it? Maybe people would look at their experience and still regard the tomato as something less than fatal if consumed - but still something toxic and bad to eat. And then they would have been wrong, without knowing what the whole story was.

One of the first flaws in using anecdotal evidence is not being able to consider all the variables that affect one's condition and the outcome. In order for anecdotal evidence to have more value, other variables must be eliminated to make sure of the truth.

Looking at the problem of the tomato and the first person who got sick after eating it, one can come up with the following basic question:

How can you be so sure it was a toxin in the tomato that caused their symptoms?

They could have done any of the following:

• Eaten a bad piece of fish an hour before they ate the tomato, and the fish really made them sick.
• Contracted a stomach flu or virus from their next door neighbor, and that made them sick.
• Eaten an insect that was within the tomato that didn't agree with them.
• Had a small amount of mold or fungus on the tomato that didn't agree with them.
• Been unlucky enough to eat a tomato that was a bad tomato - not ripe enough, or somewhat overripe; perhaps bordering on rotten.
• Had an allergic reaction to the tomato itself.
• Had a medical condition that was completely unrelated to anything they ate or a passing viral infection.

So, one can think of a number of reasons why someone could have eaten a tomato and got ill afterwards - but each of these reasons has nothing to do with the tomato itself being a toxic food.

Without knowing any of these potential reasons, from external observation, one could be led to follow simple cause and effect, where the person observed to have eaten the tomato got sick shortly thereafter and everyone assumed during that time that toxins in the tomato was the reason why.

Well, you know what they say: Never assume, because then you make an...

Anyway, eventually someone else probably heard that others enjoyed eating tomatoes in other countries and lived quite long and fruitful lives despite this, and tried eating a tomato and didn't have any problems. Once enough people began eating tomatoes and not puking their guts out or dropping like flies, then more people felt willing to try eating them - even if they might later turned out to have had a serious allergy to them, at worst - or decided they just didn't like them, at best.

In the end,  most people on the planet have had the experience of eating a tomato by now and most of them don't get horribly ill from consuming them.

It might have taken a while to build up enough anecdotal evidence to convince people that tomatoes were safe to eat. After all, people were convinced for a long time that they were poisonous, and any of the above issues listed may have led to people getting ill around the eating of a tomato. It was probably clearer tomatoes were okay if the people eating them weren't also coming down with the stomach 'flu', washed their tomato before eating it, and they hadn't eaten anything else all day.

So, tomatoes are, by and large, safe to eat - and many would say they're quite tasty, too. (I do.)

Let's talk about ancedotal evidence using the tomato in another way, though - by making a claim.


What if a person were to say, "I feel so much better after eating this tomato," or even "Symptom x has improved ever since I ate a tomato."

Well, I admit that many times after I've eaten a tomato, I feel better, too - but usually it's because I've been starving and finally had something to eat. And it was tasty. And filling. Which brings me a certain amount of emotional and physical satisfaction.

But once I begin saying something as specific as, "Symptom x has improved ever since I ate a tomato", well, then that provokes a question in response to that claim:

How can you be so sure it was the tomato that caused symptom x to improve?

The person who ate the tomato could have done any of the following or had them happen to them:

• Had a temporary improvement in that symptom based on the usual ups and downs of their condition.
• Had a lasting improvement that occurred for reasons unknown to anyone.
• Experienced an improvement due to some medication they'd already been taking over time, and just noticed a distinct improvement after eating the tomato.
• Experienced an improvement due to some medication they'd started recently.
• Experienced an improvement due to some other supplement or food they'd been consuming over time, and just noticed a distinct improvement after eating the tomato.
• Experienced an improvement due to some other supplement or food they'd started consuming recently.
• Experienced improvement because of their frame of mind - belief in the tomato making them feel better actually led to them feeling better. (Also known as the placebo effect.)

And of course, it is possible that symptom x really did improve because they ate that tomato, but then: How would you know?

The only way you could know for certain would be to eliminate all the other variables as much as one possibly could, and test it. Find some way to measure the improvement in symptom x in that person, and eliminate the other variables - then go on to repeat that experiment with a larger group of people.

To be sure that it is the tomato that is leading to symptom improvement, the highest test of the tomato-causes-symptom-x-improvement-hypothesis is to give a fairly homogenous group of people with symptom x (where the above variables are eliminated) a tomato and measure improvement in symptom x post-consumption, and to give another fairly homogeous group of people with symptom x (where the above variables are eliminated) a non-tomato placebo that looks and tastes like a tomato and measure improvement in symptom x post-consumption of that placebo.

Next, don't tell which group has the real tomatoes and which group has the fake or placebo tomatoes. Better yet: Don't even tell the scientists running the experiment who has the real tomatoes and the fake ones, either. That way, when scientists come around to record data from the patients, they can't accidentally let slip in conversation or body language whether or not the patients in front of them are consuming the real tomatoes or the fake ones. They don't know anything about it. So they can't influence the outcome much.

This is what double blind studies are all about - and with them, it's supposed to be easier to obtain more reliable evidence that a particular treatment works (or not).

One of the problems with discussion of improvement of subjective symptoms - such as reporting "I feel better", or "symptom x is better", is that they do not make good outcome measures.

How do you measure them? Where do you draw a line in the sand between, say, pain that is a 6 out of 10 in one person compared to pain that is a 6 out of 10 in the next? What does '5' mean? (Ask Allie - she'll tell you what she thinks it means.) Does one person count having a runny nose as having a cold? If that person takes some Vitamin C, thinking it will help them avoid colds, they might dismiss their runny nose and report (and even remember) that they did not get any colds while taking the treatment.

One thing scientists have said all along is this: The plural of anecdote is anecdotes - not data. 

One has to come up with a well-defined set of criteria that can be consistently measured across a larger population in studies, and subjective reporting is often a problem given the examples above.

So, knowing all of this, what is the person who has already tried all of the tried-and-true, scientifically-studied treatments going to do?

What if one is a Lyme disease (and other tickborne infections) patient and has already blown through a number of antibiotics and is still symptomatic?

These questions and more will be addressed in part 2.

This work by Camp Other is licensed under a Creative Commons
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2 The Friday Four

1) Stress affects the balance of bacteria in the gut and immune response

Low stress & bacterial biodiversity:
The key to better health?

ScienceDaily (2011-03-22) -- Stress can change the balance of bacteria that naturally live in the gut, according to new research.

This study funded by the NIH shows that stress dysregulates the immune system, changing the natural flora of one's intestines and leaving people more susceptible to infections such as C. difficile. The more biodiverse intestinal flora is, the healthier one's immune system generally is.

Intestinal bacteria have been linked to diseases like inflammatory bowel disease and asthma, and a future goal of the study is see if changes in gut bacteria is related to such diseases worsening when people are under more pressure.

Comments:

Lyme disease patients are already pretty savvy about taking probiotics inbetween taking antibiotics - but is there something that can be done to diversify the number and kind of bacteria in our guts that would reflect the right balance of helpful organisms? Which combination of organisms is most beneficial to have, and how close are common probiotic blends to this beneficial mix?

Original Source Reference:
Bailey. Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation? Brain, Behavior, and Immunity, 2011; 25 (3): 397 DOI: 10.1016/j.bbi.2010.10.023

2) 'Knowing it in your gut' is real: Cross-talk between human gut bacteria and brain

ScienceDaily (2011-03-23) -- A lot of chatter goes on inside each one of us and not all of it happens between our ears. Researchers have discovered that the "cross-talk" between bacteria in our gut and our brain plays an important role in the development of psychiatric illness, intestinal diseases and probably other health problems as well including obesity.

This study showed that genes linked to learning and memory are altered in germ-free mice and, in particular, in the hippocampus - one of the key brain regions for learning and memory.

"The take-home message is that gut bacteria influences anxiety-like behavior through alterations in the way the brain is wired," said Jane Foster, associate professor in the Department of Psychiatry and Behavioural Neurosciences of the Michael G. DeGroote School of Medicine.

Foster's team has a hypothesis that the state of your immune system and your gut bacteria influence your personality - and in this case, influences anxiety.

Comments:

This reminds me of a video I posted in a Friday Four a while ago that showed personality changes in mice based on whether they had cultivated bacteria or not.

One fascinating thing to consider here is if researchers find out that certain bacterial flora combinations create different psychological states and can be directly implicated in mental illness that new treatments involving probiotics may improve conditions that to date have been treated with psychiatric medications. Perhaps these new treatments will avoid some of the more troubling side effects of anti-depressants and anti-psychotic drugs.

Original Source Reference:
K. M. Neufeld, N. Kang, J. Bienenstock, J. A. Foster.Reduced anxiety-like behavior and central neurochemical change in germ-free mice.Neurogastroenterology & Motility, 2011; 23 (3): 255 DOI:10.1111/j.1365-2982.2010.01620.x

3) Biofilm  reorganization: Back to the theoretical drawing board

Staphlococcus aureus biofilm

"In a surprising new study, researchers using image-analysis methods similar to those employed in facial-recognition software have made a startling discovery that rules out the two main theories scientists had created to explain how bacteria self-organize into multicellular aggregate mounds. The study by researchers from Rice University and the University of Georgia has implications for biofilm research and appears online this week in the Proceedings of the National Academy of Sciences."

What scientists did was make a microscopic movie of Myxococcus xanthus, common soil bacteria, while it was forming aggregates or spore forms with up to 100,000 cells. In this way, the bacteria could survive more easily - just as many other bacteria survive in biofilms to evade antibiotics.

They discovered that the size of the aggregates led to a higher survival rate, and not other factors they predicted such as individual chemical signaling between cells.

So in this case: size matters.

Comments:

More studies on how biofilms form and what can be done to break them up are needed to prevent resistant infections. Studying bacteria and how it organizes itself can tell us more about what makes biofilms work and how to target them for treatment in the future.

4) Breakthrough in delivering drugs to the brain

Alzheimer's plaque

A team of researchers Oxford removed exosomes from mouse dentritic (immune system) cells. Then they attached specific proteins from the rabies virus (not the virus itself) to these exosomes -  proteins which bind to acetylcholine receptors in brain cells.

Then they filled these exosomes with the genetic code, siRNA, and injected them back into the mice.

In doing so, the siRNA got delivered to the mice's brain cells and turned off a gene (BACE1) which is involved in Alzheimer's disease. There was a 60% reduction in the gene's activity.

Comments:

If there is more than one cause for Alzheimer's disease - if it can be treated by using the body's own natural defenses and systems - this could be ground breaking.

Treatment systems similar to these exosome injections could also potentially be used to deliver medicine past the blood brain barrier for other conditions including cancer and infectious diseases.

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0 Video: Immunology Lectures from The Einstein College of Medicine

Given the volume of questions I'm getting on the immune system lately, I thought I'd post this 14 part mini series on the immune system.

Others have reported that watching this makes learning about immunology less scary and overwhelming - I haven't seen the entire series yet, but how about watching an episode or two and letting me know what you think of them?

There are slides online which accompany the lectures - these are the first session's slides:

http://www.einstein.yu.edu/multimedia/videos/conferences/immunologycourseinsouthafrica/L-1-Goldstein-Componenets-of-immune-system.pdf

Below is episode 1 - from there you should be able to advance to the next video in the series.

Learning more about immunology, microbiology, genetics, and molecular biology will help in understanding the research that is out there as well as patents.

All this knowledge is within reach - but requires putting the time in, and patience with one's own brain fog. I know, because I've been there... and it's a slow learning process - but learning does happen.

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27 What happened? The Early Days of Lyme Disease

This could end up being part of a series on the history of Lyme disease, but for now I wanted to share something from Polly Murray's book, The Widening Circle.

I really can't recommend this book enough for readers who are either Lyme patients or care about someone who is a patient - it is a well-written account of one woman's journey of struggling with strange symptoms that were plaguing her and her family for years. Her determination to find the cause, and how her actions led to the discovery of Borrelia burgdorferi in ticks led to all that people in the Lyme disease patient community are familiar with now.

Gandhi once said, "Be the change you wish to see in this world," and I think Ms. Murray's life reflects that statement.

Moving on to the question of "What happened?" in regards to how the introduction of Lyme disease back then led to the state of affairs over Lyme disease now (which is something people ask whenever they read the 1993 Senate testimony I recently posted): It's not that easily answered.

A combination of physicians who weren't sure how to treat Lyme disease not long after the disease had been discovered, physicians who came down ill themselves and self-treated for longer if their symptoms relapsed, the media's role in educating the public about Lyme disease leading to fearful patients, politicians in Connecticut who were slow to respond to patient demands for improvements in diagnosing and reporting the disease - all of these contributed to the atmosphere around Lyme disease.

The slow response of politicians and doctors to increasing numbers of patients suffering from Lyme disease led to the creation and growth of Lyme disease patient support groups. Even back then, by 1992 there were over 100 patient support groups for Lyme disease.

I quote an excerpt from Polly Murray's The Widening Circle, pages 266-267:

"Some doctors I have encountered think that Lyme disease is easily treated by a single course of antibiotics in its early stages; if patients fail to overcome the infection after one treatment, their future complaints are considered to be not associated with Lyme disease. These doctors believe that once a patient is treated, he or she no longer has Lyme disease.

In 1987-1988, tremendous media attention was given to the disease; I think this was generally beneficial. Correct information must prevail over ignorance. However, when the public saw the grave outcomes suffered by the patients who appeared on TV, many were scared that if they were bitten by a tick, they would have devastating illness. While a number of people do not respond to treatment or have not had treatment and have had severe complications, a proportionately far greater number are treated and seem to do well. (It is true, however, that some may relapse or enter another stage of the disease, sometimes many years later.)

Some doctors during this period of media attention were inundated by people worried that they might have the disease; they called this anxiety Lyme hysteria and Lyme paranoia. Some patients, as I have mentioned, were told they were "antibiotic junkies". There seemed to be many extremes in attitude, some physicians being unwilling to diagnose Lyme disease even with a classic presentation, and others willing to treat anyone with any vague symptom for Lyme disease. The unreliability of Lyme tests, as we shall see, did not help matters."

So, during this time, according to Polly Murray's account, people who were incredibly sick with Lyme disease were in the media spotlight and it led to fear in many people. The fear was not entirely unfounded - people do suffer greatly from Lyme disease. But if caught early, a significant number of patients go on to do well.

Why this is remains a complicated answer, and something that this blog investigates over time - it won't be limited to a paragraph or two of text.

At any rate, some people were afraid they had Lyme disease, and rather than be compassionate, some of these doctors were making negative statements about such patients. How many, I don't know - Ms. Murray doesn't elaborate on numbers.

It definitely does seem as if there was a greater mix of opinions in the medical profession about how to diagnose and treat Lyme disease. It was less monolithic, and the push from a handful of select professional medical organizations to set the standard of care for all primary care physicians wasn't in place yet.

Ms. Murray continued:

"A number of physicians continued to say that media hype was distorting the true profile of Lyme disease and was scaring people unnecessarily. True, the adverse outcomes were proportionately rare; however, to the rare patient with a devastating outcome, statistics are irrelevant. The fact remains that the more proper information citizens and physicians are armed with, the more likely they will be to protect themselves from Lyme infection and to detect and treat Lyme disease early so that devastating outcomes will be less likely.

As the number of cases continued to rise, some physicians in endemic areas began to see great numbers of patients with Lyme disease. With their growing experience, many of these physicians became convinced that suggested treatment regimens were insufficient to combat the disease in some cases and were calling for longer and more aggressive treatment. They began to encounter patients who clinically seemed to have Lyme yet tested negative, while a number of patients continued to have persistent symptoms and remained chronically ill for years despite treatment. This area of chronic complications is the most controversial and the most disheartening part of the Lyme disease story."

So as the number of cases went up, so did the number of patients who had seronegative Lyme disease and those who seemed to have a condition resistant to treatment.

To get a complete picture of how a disease is going to interact with a population, one can extrapolate what percentage will be infected from a smaller sample size - but it's harder when the presentation is not consistent across the board. Harder when a disease can be seronegative. Harder when it's suspected a disease can be asymptomatic and latent, only to present in its third, most serious stage later.

Part of what fueled the controversy back then was research in 1989 by V. Preac-Mursic and also doctors who were infected with Lyme disease who self-treated themselves longer than what Yale's suggested guidelines were at the time (that 2-4 week treatment length everyone in Lyme world is familiar with).

Ms. Murray wrote,

"Evidence has been found for the persistence of the spirochete in various parts of the body, despite antibiotic treatment and negative tests. A 1990 paper by V. Preac-Mursic and colleagues reported studies of patients who had originally been seropostiive, had been treated with antibiotics, and then had become seronegative. However, spirochetes could be cultured from skin specimens and spinal fluid from these patients, showing a persistence of the infection. In her summary, Dr. Preac-Mursic said, 'We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B. burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B. burgdorferi from CSF [cerebrospinal fluid] and skin biopsy in our patients after antibiotic therapy with normal CSF-values and negative serological tests for B. burgdorferi raises important considerations in the treatment of Lyme borreliosis.' Indeed, this study raises important questions as to both the adequacy of antibiotics in treating the disease and the reliability of the tests in detecting the disease."

The above mentioned study, for the curious, is this one:
PREAC-MURSIC V, WEBER K, PFISTER HW et al.: Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection (1989) 17:355-359.

To see the abstract for this paper (about halfway down the page) and papers with similar focus, I recommend this collection of links found at Lymenet Germany:
http://www.lymenet.de/literatur/niches.htm

There's a lot of science information on the Lymenet Germany web site - much of it in English - so I recommend checking it out some time.

Anyway, knowing this and other research about persistence only fueled the controversy at this time.

By the time 1992 rolled around, and the Fifth International Conference on Lyme Disease was held, the controversy was present at the conference itself.

As Murray reported:

"A number of papers submitted by physicians in endemic areas had been rejected by the conference's program committee. After protests from support groups and patients concerned that important new information on the disease was being excluded, the committee reversed its decision."

Does this sound familiar at all to any of you reading right now? Like maybe how things went down with the October 2010 Institute of Medicine workshop on tickborne illness?

She continued:

"It was my feelings that the patients who attended the conference primarily wanted better research and information on treatment evaluation and the development of more effective therapies and techniques of prevention. They were obviously interested in a cure. Many had found that the prescribed four-week treatment with antibiotics was not sufficient, and that they relapsed if not treated for long enough period of time. They questioned commonly accepted paradigms of the illness and believed that important questions were not being investigated."

And later on,

"After the conference a number of patient representatives wrote to its heads, citing six papers presented at the meeting which endorsed the theory that the spirochete persisted even after treatment and that a patient could be seronegative and yet have Lyme disease. They 'asked for more research on pathogenesis, long-term antibiotics and innovative drug delivery systems' and 'offered their services as participants in an NIH-sponsored effort to find a cure for chronic Lyme disease.'

Those patients sound just like me! That's what I'm asking for, too - more research on pathogenesis, long-term antibiotics, and innovative drug delivery systems.

Whoa.

So, as you can see, the issue of Lyme disease and its treatment being controversial has been with us for many years. The problems and concerns which patients faced twenty years ago are, sadly, the same problems and concerns they face today.

Where do we go next? What can patients do to change this state of affairs without reinventing the wheel?

A lot of awareness has been raised about Lyme disease in recent years - the publishing of Cure Unknown, the making and distribution of the film, Under Our Skin; the increasing online presence of large scale Lyme disease patient social networking sites, and numerous campaigns, fundraising drives, and events have been held to get more attention for Lyme disease.

How much this helps towards getting the research that is so badly needed remains to be seen. The funding and development of the Columbia University Lyme and Tickborne Diseases Research Center is definitely one of the bright spots in the Lyme patient community, but more such spots are needed and were needed years ago.

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18 1993 Senate Testimony On Lyme Disease, Part 2

In Part 1, 1993 Senate testimony on Lyme disease given by Dr. Joe Burrascano was posted for review. In this part, various excerpts from Steere, other researchers, and others on the Senate committee will be reviewed with comments and questions.

As much as I know the Lyme patient community disdains Steere, and as much as I consider his March 2010 slideshow disrespectful of patients, there are a few places in this testimony where I found myself actually shaking my head in agreement with what he said back in 1993.

See what you think...

Alan Steere said:

"Research is certainly needed to improve laboratory tests
for Lyme disease, particularly for the development of tests
that detect the spirochete or its genes or antigens directly. 
However, improved laboratory tests will not by themselves
solve the problem of Lyme disease diagnosis. I believe that
clinical judgment will always be necessary."

I agree with him there.

Senator Dodd. Just let me get an answer to this,
and I'd be glad to. 

Do you think we ought to spend money on it?

Dr. Steere. Yes, absolutely. I think that Lyme disease is a great 
problem, and I think studies of it, particularly basic mechanisms 
of the disease, are of great importance. And I think that's what is 
most likely to help.

Again, I agree with this. Let's look at some more testimony and exchange with the senators...

Senator Metzenbaum. Thank you, Mr. Chairman. I have a cou- 
ple questions. 

Dr. Steere, I gather that the diagnosis of Lyme disease is not 
that fully developed that the physicians around the country really 
know enough about it or know enough about how to make the diag- 
nosis. Is that the thrust of what you are saying? 

Dr. Steere. I think that there are objective clinical criteria. I 
also think that it is possible to have laboratory tests that can help 
support that diagnosis. But nationwide, there is no standardization 
of that type of testing. 

There is certainly a great need for education, including education 
of physicians, about what this disease is and what it is like. And 
certainly, further research is needed to define that even more. 

Senator Metzenbaum. I remember when one of our fellow Mem- 
bers of Congress was diagnosed as having Lyme disease, Berkeley 
Bidell, a fine member of this body, and he resigned — or stepped out 
and didn't run for re-election; I guess he didn't actually resign — be- 
cause he thought he had Lyme disease, and subsequently found he 
did not. 

I get the feeling that across this broad United States, if you go 
to see Dr. Steere or one of these other gentlemen here, that you 
probably can get an accurate answer, but that there is a reasonable 
chance that if you go to many other doctors in the country — and 
this is not a broad-brush condemnation of them — but that it is not 
easily diagnosed and not easily diagnosed even after laboratory 
tests, unless the laboratories are particularly prepared for this kind 
of diagnosis. 

Now, am I misinterpreting what you are saying? 

Dr. Steere. No. I think that is absolutely true and very well-
stated.

Senator Metzenbaum. So therefore we have the problem of how 
we get the education out and how we get the diagnosis out. 

Now with respect to the treatment, you mentioned two particular 
products that can be used— I forget what they were; I'm sure you 
know what they are — with oral 

Dr. Steere. Oral therapy with doxycycline, a tetracycline type of 
antibiotic, and amoxicillin, a penicillin type of antibiotic. 

Senator Metzenbaum. And how effective is that? 

Dr. Steere. Well, I think for nonneurologic manifestations of the 
disease, they are quite effective. Neurologic manifestations of the 
disease are harder to treat, and how best to treat them is still 
being worked out.

Italics emphasis mine.

I think everything italicized is something that is important to note... The same problems Steere mentioned back in 1993 are the same problems the Lyme patient community is facing today.

I don't agree with Steere on everything, but I do think what he said back then is still true today.

Does anyone know how standardized today's testing is?

I think more studies of the basic mechanism of the disease would help a lot - quite possibly the most, too.

How much of our tax money has gone towards basic science research on pathogenesis and study of the spirochete versus other research? This is something a lot of people are asking, and not just me.

The other points Steere mentioned - that more first-line doctors such as primary care physicians need to be better educated to diagnose and treat early Lyme disease and that how best to treat neurological Lyme disease needs to be worked out - both of those are issues which I think still haven't been adequately addressed in the 18 years since he stated them.

There is other testimony there about serological testing and exchanges with Burrascano I'm not going to get into right now, some of which I disagree with Steere based on what research I've read thus far. These particular passages have been discussed in the Lyme patient community before, so I'm going to move on to other testimony by others...

Dr. BURRASCANO. The second point I wanted to address was the 
Simplification of the treatment ot Lyme disease Many patients who 
have been diagnosed after the disease has been present for more 
than just a short period of time, those who have had the illness for 
several months to several years before diagnosis, very often are not 
returned back to normal with antibiotic therapy as we know it 
today. 

One of the problems is that we don't know why people remain 
ill. We pretty much recognize that a lot of people will remain ill 
after Short courses of antibiotic therapy when they have late 
disseminated Lyme disease. The controversy which I tried to address 
today in my testimony is that we don't know why. 

There is an establishment of physicians university based who 
claim that the 30 days of treatment cures the patients; anything 
that is leftover has to be some arthritic phenomenon or some- 
thing they don't knew what it is and they send the patients off 
to a chronic fatigue clinic or to a fibromyalgia clinic. Yet there have 
now been many, many studies showing that these people still have 
the infection. 

So apparently, the infection can persist and evade the effects of 
antibiotics, and the presence of the organism somehow drives this 
reaction to keep the people sick. 

I have here an electron micrograph, a photograph of the spiro- 
chete, done by the NIH's lab at Rocky Mountain. This was taken 
from the urine of a patient who remained ill after one and a half 
years of antibiotics. This spirochete was identified positively as B. 
burgdorferi, the causative agent for Lyme disease. So in this one 
patient — and again, there are patients that you might see in the 
audience or who have testified today who are in a similar situa- 
tion — for them, the antibiotic therapy did not work. 

So what I am saying is that we need to focus our research on 
the real world of Lyme disease. No. 1, diagnosis is not simple or 
clear; the diagnostic test is not 100 percent. We need better testing. 
No. 2, treatment strategies as you might find in New England 
Journal articles are very basic minimums and do not cover the 
more chronic patients or those who are more seriously ill, and 
these chronic patients are not now being studied systematically for 
infection, and they should be."

Is evidence of a spirochete found in urine at the NIH's lab considered a significant finding? Why or why not?

Is evidence of Bb DNA found in a sample significant - why or why not?

In the discussion of findings from various research publications, it's been stated that finding bacterial DNA is not evidence of current infection. Finding a live, whole organism can be, though.

Here's some excerpts from Dr. Joe McDade... introduction included so you know who he is:

STATEMENTS OF DR. JOSEPH McDADE, ASSOCIATE DIRECTOR 
OF LABORATORY SCIENCE, NATIONAL CENTER FOR INFEC- 
TIOUS DISEASES, CENTERS FOR DISEASE CONTROL AND 
PREVENTION, ATLANTA, GA; AND JOHN R. LAMONTAGNE, DI- 
RECTOR, DIVISION OF MICROBIOLOGY AND INFECTIOUS 
DISEASES, NATIONAL INSTITUTE OF ALLERGY AND INFEC- 
TIOUS DISEASES, NATIONAL INSTITUTES OF HEALTH, BE- 
THESDA,MD 

[...]

Dr. McDade. I certainly will do that. I think that the most im- 
portant problem that we have is a lack of recognition of Lyme dis- 
ease by the average physician. A recent CDC study in a north- 
eastern State showed that 82 percent of the cases of Lyme disease 
were reported by 7 percent of the physicians. 

Now, there are different ways of interpreting this data, but this 
was from a State in which Lyme disease is broadly endemic, and 
what that suggests is 

Senator Dodd. Which State are we talking about? 

Dr. McDade. Connecticut. 

Senator Dodd. I was afraid of that. [Laughter.] There are a lot 
of States in the Northeast, and so I was hoping 

Dr. McDade. It is not meant at all as an indictment of Connecti- 
cut. It probably reflects the situation nationwide, which is that ei- 
ther people are not reporting Lyme disease, or they aren't recogniz- 
ing it. And if they are not recognizing it, and they are not treating 
it early — and you have heard adequate testimony to this point — we 
have a serious problem. 

So to my mind, the physician awareness and education of the 
professionals is a key critical component, one that we have been 
working on and that needs a lot more attention. 

The second problem is one of diagnosis. This has been adequately 
documented and today, in testimony from a number of panelists, 
and clearly what it amounts to is a need for increased standardiza- 
tion and there is a need for increased research. CDC has been 
working in the last several months with the Association of State 
and Territorial Public Health Laboratory Directors to standardize 
some of the existing methodology, and that is currently under eval- 
uation. 

So, sounds like the same things that Burrascano and Steere said were a problem are problem in McDade's eyes, too.

To my readers in Connecticut: Do you have any research and evidence that reflects improvement in how many Connecticut doctors are accurately diagnosing and treating Lyme disease in the present and last few years?

I hope it has improved since 1993. That rate cited above - 7%? Sucks.

Dr. McDade. [...] But I think the point is that every- 
one recognizes that there are some deficiencies in the diagnostic 
criteria. The point is where do we go from here. I think there are 
in fact two different kinds of deficiencies. One is the lack of stand- 
ardization in evaluation of the existing methodologies. As I indi- 
cated, we have been working with the Association of State and Ter- 
ritorial Laboratory Directors to standardize what we have so that 
we can at least look uniformly across the States. 

Clearly, there are also many other things that are on the horizon 
that are being studied both by CDC intramurally, our extramural 
program, the NIH extramural program, which offer a lot of better 
alternatives. 

What wasn't perhaps said in some detail, without going into de- 
tails of the science, is that we are dealing with a very worthy ad- 
versary in B. burgdorferi. There are multiple strains of this orga- 
nism; it undergoes antigenic variation, and any diagnostic test that 
you have is going to be fraught with some difficulties. So this is not 
an easy problem, and everyone who is doing research on this recog- 
nizes these problems and is working toward them. But clearly, 
what we need to do is to employ our best efforts to try to find out 
which ones are there and which ones work in a real life situation. 

Here is where I wish McDade would have gone, actually - into details of the science behind B. burgdorferi. He is saying difference in strain and antigenic variation are an issue; that diagnostic tests are fraught with difficulties. I wish he would have gotten into more specifics here.

Senator Metzenbaum. Doctor, can I ask you, has CDC done any- 
thing about notifying the doctors of this country what to look for 
with respect to Lyme disease and what kind of testing is suggested 
in order to deal with it? 

I get the feeling that some doctors know about this, but there are 
a hell of a lot of doctors out there who don't know anything about 
it and just sort of push along. Am I wrong about that? Are you pro- 
viding information, or what is the fact? 

Dr. McDade. I think education is coming from a variety of 
sources, as was indicated earlier. For education of children, one of 
our cooperative agreements with the Lyme Disease Foundation — 
they have reached millions of people. Also, I can provide for the 
record if you like a list of the extramural funding; there are some 
half dozen various projects that are targeted directly or indirectly 
toward physician education. That is not to mention the general lit- 
erature, three or four articles published weekly by our Morbidity 
and Mortality Weekly Report, that address various issues, be they 
clinical, epidemiologic, prevention and control. 

There are a number of different approaches that are used. But 
as I'm sure you well can realize, any message that you might try 
to deliver, be it in the commercial sector, private sector, education- 
ally, or in medical, it is sometimes very difficult to reach 100 per- 
cent of the population, and it becomes more costly as you try to get 
100 percent awareness. 

Senator Metzenbaum. What I understand you to say is that doc- 
tors can find this information in a lot of places — in the journals and 
the medical literature — but that the Centers for Disease Control it- 
self has really — I think all of those hit a certain portion of the doc- 
tors of the country — but it seems to me that the CDC, without 
spending a fantastic amount of money, could do a much more effec- 
tive job of really getting to all the doctors in the country. 

Dr. McDade. We certainly don't at all think, Senator, that what 
we have done is enough, and we will continue to look at other ap- 
proaches and other venues in order to try to leverage resources to 
be able to reach the people maximally. I think that's about the 
most general way that I can State it. 

We are very aware not only of what we have done, but more 
aware of what we have not done. 

That sounds a lot like admitting that more could have been done when it wasn't, doesn't it?

Senator Metzenbaum. As I sit here, I get the feeling that this 
is a very challenging kind of illness or disease, but the fact is there 
is much more that can be done about it than we can do about a 
number of other illnesses, whether it is cancer or some other dis- 
ease of that kind. And what is bothering me is that I just have the 
feeling that there is a gap where the physicians in the field are 
really not up-to-speed as to diagnosis and treatment. And I think 
Dr. Steere pretty much confirmed that. And I think CDC is the 
agency to which we in Congress would look to ask, don't you have 
a greater responsibility than that which you are presently doing. 

Dr. McDade. I can say that your statement is entirely accurate, 
and CDC would love to have the opportunity to meet that chal- 
lenge.

Testimony immediately after this section goes on to discuss the recommendation that Dr. McDade request more funding from the gov't for the CDC to address this issue... Need to follow up to see exactly what happened after this, and where the funding was applied.

It seems to me that the exact same issues that concerned people in 1993 are still with us.

And now, onto Mr. LaMontagne's testimony...

[...]

Mr. LaMontagne. Lyme disease is now thought to be the most 
commonly reported arthropod-borne disease in the United States — it is 
certainly the most common tick-borne infection in the United States. 
The disease, caused by the spirochete B. burgdorferi, is transmitted 
primarily by ticks of the genus Ixodes. Lyme disease may be 
acute or self-limited or may develop into a chronic multisystem 
disease that can elicit a wide and unpredictable range of clinical 
manifestations. Current diagnostic tests, which are based on the 
detection of antibodies to B. burgdorferi, are useful, but far 
from perfect since individuals may vary widely in their immunological
response to infection, thus limiting the value of blood test 
results In the diagnostic process. 

As indicated, Lyme disease does not have a predictable clinical 
presentation or progression of symptoms. Most persons infected 
with B. burgdorferi respond to infection with strong immune 
responses, whereas others show no sign of infection in 
their blood. The organism also is very difficult and in some 
cases impossible to detect in infected individuals. Many published
descriptions indicate that the hallmark of Lyme disease is an
expanding red rash, known as erythema migrans, that may 
be accompanied by various other clinical signs and symptoms. 
Infected individuals actually present a highly variable array
of signs and symptoms, such as joint pain and nerve problems, 
that may be easily confused with those of other diseases. The 
ambiguities inherent in interpreting the results of blood tests 
for Lyme disease added to these nonspecific symptoms have led
to problems with both over- and under-diagnosis of the disease.

NIAID currently conducts and supports several projects
aimed at meeting the challenges of Lyme disease. Institute
goals for this area of research include: 

Improve our understanding of the immune response of infected 
individuals to B. burgdorferi. 

Improve our understanding of the biology and surface 
variation of B. burgdorferi. 

Develop tissue culture models of Lyme disease. 

Develop animal models of Lyme disease. 

Identify and characterize virulence factors and 
antigenic determinants of B. burgdorferi. 

Develop improved diagnostic and therapeutic strategies. 

Develop an effective human vaccine. 

Study the host range of B. burgdorferi in potential 
vector (transmitter) and reservoir (carrier) species. 

Study the biology and ecology of vector and 
reservoir species. 

Develop strategies for the control of Lyme disease 
transmission among reservoir species and to humans. 

I would like to take this opportunity to highlight for 
you recent advances made in our intramural and 
extramural programs and to briefly outline our research 
plans for the near future.

NIAID Intramural Research Program

INTRAMURAL RESEARCH ADVANCES 

Several NIAID scientists conduct Lyme disease research 
studies at the RML. Highlights of some of their recent 
efforts are summarized below. 

Scientists at RML have developed a highly sensitive 
and specific method to detect B. burgdorferi infection.
The assay works well with samples of urine, cerebrospinal fluid,
blood, and synovial fluid. Because the assay detects 
components of the infecting spirochetes rather than
immune responses to it, if it can be developed commercially,
the assay may prove useful for monitoring treatment
effectiveness as well.

A major stumbling block to developing diagnostic 
tests or a vaccine for Lyme disease is the elusive 
nature of the spirochete. The organism appears to evade the
immune system of the host by changing its surface proteins. 
NIAID scientists are studying changes in genes encoding 
two major outer membrane proteins of the spirochete. The 
studies may provide insights into the surface proteins of not only 
B.burgdorferi but also other borrelia organisms as well. 

NIAID'S researchers have genetically characterized samples
of Lyme disease bacteria taken from many patients in Europe, 
Asia, and North America. Based on genetic relatedness, the 
scientists have identified at least three distinct groups
of borreliae that can cause Lyme disease. The frequency
with which different Lyme disease symptoms occurs is 
known to vary in different geographic areas. The sci- 
entists have begun examining how the genetic distinctions 
within each group relate to clinical features of Lyme disease.

NIAID research recently showed that antibodies to 
a specific protein of the spirochete, p39, are produced 
only in response to an active B. burgdorferi infection 
and therefore can serve as reliable markers for Lyme disease. 
Using this observation, the researchers have developed 
three p39-based blood test kits that can help distinguish 
patients with Lyme disease from those with other disorders.

These kits have been approved by the Food and Drug Administration 
and are currently available to doctors, clinics, and 
hospitals nationwide. 

Scientists at the RML have demonstrated a characteristic of B. 
burgdorferi that may explain its ability to cluster in low 
numbers at the site of infection and yet cause a variety of 
reactions at other sites in the body. B. burgdorferi cells
release pouches or "blebs" from their surface that become distributed
widely throughout the body, unleashing a variety of immune system 
and tissue responses that may result in the diverse symptoms
seen in Lyme disease patients.

Coumermycin Al is an antibiotic that inhibits the enzyme
that catalyzes the coiling of DNA molecules and is required 
for bacterial replication and growth. Since the Lyme disease
spirochete has coiled molecules, NIAID investigators tested
the activity of this antibiotic on B. burgdorferi. They
found the Lyme disease spirochete to be 100 times more 
sensitive than other bacteria to this compound.

Although coumermycin Al or similar drugs are not ready
to be tested in humans, this research indicates that such
drugs should be investigated and developed further as 
potential therapies for human Lyme disease.

FUTURE PLANS 

The following future plans will be emphasized by NIAID
intramural scientists: 

Improve the sensitivity of the blood test kits and 
other available diagnostic tools. 

Continue studies of the variation and biological effect of 
Borrelial surface proteins with the goal of developing
an effective vaccine. 

Examine the attachment and penetration of spirochetes into
human cells as a possible mechanism of maintaining 
chronic infection. 

Examine the role of ticks in the maintenance and delivery
of the pathogen.

I realize that 18 years ago is a while ago, but what happened to some of this research?

Does anyone reading this know which assay they were talking about above, and if it was abandoned because of the previously stated idea that the presence of spirochetal DNA does not indicate the presence of current infection?

Is the evidence of a living spirochete the only indication of active infection? It seems there has been some argument in the literature between whether or not a small number of intact spirochetes can cause an infection and this hasn't been completely resolved. It definitely seems that serological testing isn't enough for some people.

From what is known today, there are more strains being found in different geographic locations than previously thought, with some vectors being birds - and also a greater number of disease-causing genotypes being found through Dr. Ben Lutz's studies... There's more work to be done there and it's ongoing.

How much research has the RML conducted on these pouches or bleb forms since then?

According to Tom Grier, "This bacteria replicates specific genes, and inserts them into its own cell wall, and then pinches off that part of its cell membrane, and sends the bleb into the host. Why it does this we don't know. But we do know that these blebs can irritate our immune system. Dr. Claude Garon of Rocky Mountain Laboratories has shown that there is a precise mechanism that regulates the ratio of the different types of blebs that are shed."

He also wrote, "In other bacteria the appearance of blebs often means the bacteria can share genetic information between themselves. We don't know if this is possible with Borrelia species. There have been reports of a granular form of Borrelia, which can grow to full size spirochetes, and reproduce. These granules are so small that they can be filtered and separated from live adult spirochetes by means of a micro-pore filter. (Stealth Pathogens, Lida Mattman Ph.D. 66)"

If these blebs are no longer considered significant, when did that change in opinion take place? Why don't we hear more about them today?

Why isn't Coumermycin Al being used to treat Lyme disease patients today, if Bb was considered 100 times more sensitive to this compound than any other bacteria?

Coumermycin is antibiotic derived from the bacteria, Streptomyces. Coumermycin, along with Novobiocin/Albamycin (Pharmacia And Upjohn), and Clorobiocin belong to a class of antibiotics known as aminocoumarins.

Years ago, Novobicin was removed from the market - this article from the 1970's indicates that 1 out of 5 people who used Panalba, an antibiotic made of Novobicin and Tetracycline combined, had allergic reactions to it and there were 12 fatalities recorded. So its use was discontinued.

Research on drugs that are aminocoumarins - and more specifically, DNA gyrase inhibitors - continues. So far, no treatment for patients with Lyme disease has come out of it.

In terms of that last bit - future plans of the NIAID scientists? I think they have done a lot of work on the second and fourth items, and some work on the first item, but really not much work on the third item at all.

I may be wrong, but that's my observation so far based on my own survey of the research done in, say, the past decade or so. I'd be glad to have someone point me towards more research on spirochetal attachment and penetration of human cells and chronic infection in general.

Those who are of a more conspiratorial bent may automatically point out that oversight of this item is deliberate. It may just be that with budgets not keeping pace with inflation and the fluctuating funds available, research teams decided to follow what was more profitable - vaccine and test kit development.

Or maybe researchers didn't even have a choice in what to research, and someone else decided where the funding was going for them - regardless of their own priorities and interests.

I understand the limits limited funding places on researchers - but I'd hope that if at some point one drops one of their goals, they can pick it up later.

What happened here? Why do so many physicians continue to miss diagnosis and treatment of early Lyme disease - is it lack of education, still, or is it that the clinical presentation is confounding so it's easy to miss even with education?

Have serological tests been standardized - and I don't mean in a Dearborn convention sense, which is its own separate and special issue - but for those tests which are outside of speciality labs, does there continue to be a wide range of result returns across the board?

What new antibiotic development has been undertaken? Funding has been present for more vaccine development, but requests for more new antibiotic development - even amid resistance concerns - were thwarted this past fiscal year.

There's a lot of questions I have to ask... if anyone else has followed the longer term arc of what I've mentioned above, please post your comments.

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7 1993 Senate Testimony On Lyme Disease, Part 1

A lot of Lyme disease patients have referred to Dr. Joe Burrascano's Lyme disease treatment guidelines over the years, and from time to time,  some will mention how Dr. B testified before the Committee on Labor and Human Resources of the US Senate back at the 1993 hearing, Lyme Disease: A Diagnostic And Treatment Dilemma - Examining The Adequacy Of Current Diagnostic Measures And Research Activities In The Prevention and Treatment Of Lyme Disease. (Y 4.L 11/4: S. Hrg. 103-285)

Curious on that last bit, for years I tried to track down his testimony in vain and was unable to find it online. Then, more recently I found the entire document on the internet archive site, found here:

http://www.archive.org/stream/lymediseasediagn00unit/lymediseasediagn00unit_djvu.txt

I also have a printed copy of the actual hearing notes in my possession to check against the online version for accuracy in transcription.

Part of why I wanted it was because so many people had mentioned his testimony but no one had actually posted it anywhere it had been mentioned, and searches online when I first got ill with Lyme disease left me empty-handed.

Now the mystery is solved. The bulk of the testimony that everyone kept mentioning without citing it was this (very minor grammatical and typo edits made - refer to original text above for comparison):

Dr. Burrascano. Thank you very much for holding this commit- 
tee meeting, and again, thank you for the very nice introduction. 

You have heard today that there are many problems in the field 
of Lyme disease, and I want to address one of the core problems 
that you may not be aware of. Some have called this the "Lyme dis- 
ease conspiracy." 

There is in this country a core group of university-based Lyme 
disease researchers and physicians whose opinions carry a great 
deal of weight. Unfortunately, many of them act unscientifically 
and unethically. They adhere to outdated, self-serving views and at- 
tempt to personally iscredit those whose opinions differ from their 
own. They exert strong, ethically questionable influence on medical 
journals, which enables them to publish and promote articles that 
are badly flawed. They work with Government agencies to bias the 
agenda of consensus meetings and have worked to exclude from 
these meetings and scientific seminars those with ultimate opin- 
ions. 

They behave this way for reasons of personal or professional gain 
and are involved in obvious conflicts of interest. This group pro- 
motes the idea that Lyme is a simple, rare illness that is easy to 
avoid, difficult to acquire, simple to diagnose, and easily treated 
and cured with 30 days or less of antibiotics. 

The truth, however, is that Lyme is the fastest-growing infec- 
tious illness in this country after AIDS, with the cost to society 
measured in the billions of dollars. It can be acquired by anyone 
who goes outdoors, and very often goes undiagnosed for months, 
years, or even forever in some patients, and can render the patient 
chronically ill and even totally disabled despite what this core 
group of physicians refers to as "adequate" therapy. 

They feel that when the patient fails to respond to their treat- 
ment regimen, which is a common occurrence, it is not because the 
treatment has failed, but because they have developed a new ill- 
ness, what they call the "post Lyme syndrome." They claim that 
this is not an infectious problem, but a rheumatologic or arthritic 
malady due to activation of the immune system. 

The fact is, this cannot be related to any consistent abnormality, 
but it can be related to a persistent infection. As further proof, vac- 
cinated animals now in the vaccine trials whose immune system 
has been activated by Lyme disease have never developed this post 
Lyme syndrome. Yet on the other hand, there is a great deal of sci- 
entific proof that persistent infection can exist in these patients be- 
cause the one-month treatment did not eradicate the infection. 

Indeed, many chronically ill patients whom these physicians 
have dismissed have gone on to respond to, positively, and even re- 
cover, when additional antibiotics are given. 

It is also interesting to me that these individuals who promote 
this so-called "post Lyme syndrome" as a form of arthritis depend 
on funding from arthritis groups and agencies to earn their liveli- 
hood. Some of them are known to have received large consulting 
fees from insurance companies to advise the companies to curtail 
coverage for any additional therapy beyond the arbitrary 30-day 
course. And this is even though the insurance companies do not do 
this for other illnesses. 

Following the lead of this group of physicians, a few State health 
departments have now begun to investigate, in a very threatening 
way, physicians who have more liberal views on Lyme disease diag- 
nosis and treatment than they do. And indeed, I have to confess 
that today I feel that I am taking a personal risk, a large one, be- 
cause I am stating these views publicly, for fear that I may suffer 
some repercussions despite the fact that many hundreds of physi- 
cians and many thousands of patients all over the world agree with 
what I am saying here today. 

Because of this bias by this inner circle, Lyme disease unfortu- 
nately is both underdiagnosed and undertreated in this country to 
the great detriment of many of our citizens. Let me address these 
individually. 
 
With underdiagnosis, the first problem is underreporting. The 
current reporting criteria for Lyme disease are inadequate and 
miss an estimated 30 to 50 percent of patients. Some States cur- 
tailed their active surveillance programs and saw an artificial drop 
in reported cases of nearly 40 percent, leading the uninformed to 
believe incorrectly that the number of new cases of Lyme is on the 
decline. 

The reporting procedure is often so cumbersome that many phy- 
sicians have never bothered to report cases at all, and some physi- 
cians who have reported a large number of cases have found them- 
selves targets of State health department investigations. Finally, 
too many physicians and Government agents rely on the notori- 
ously unreliable serologic blood test to confirm the diagnosis. 

That brings me to my second point, which is the poor diagnostic 
testing. It is very well-known that the serologic blood test for Lyme 
is insensitive, inaccurate, not standardized, and misses up to 40 
percent of cases; yet many physicians, including many of those re- 
ferred to above, and the senior staff at CDC and NIH, insist that 
if the blood test is negative, then the patient could not possibly 
have Lyme. This view is not supported by the facts. Lyme is diag- 
nosed clinically and can exist even when the blood test is negative. 

The Rocky Mountain Lab of the NIH, which is the country s best 
laboratory for Lyme research, had developed an excellent diag- 
nostic test for this illness nearly 4 years ago, but further work on 
it has been stalled. Incredibly, if not for private donations to the 
Government from the National Lyme Disease Foundation, this and 
other related research would have had to be abandoned. Yet many 
physicians believe that thousands of dollars of grant moneys al- 
ready awarded by the Government to other outside researchers is 
poorly directed, supporting work of low relevance and low priority 
to those sick with Lyme. In spite of this, their funding continues, 
and the Rocky Mountain Lab is still underfunded. 

The third point is that the university and Government-based es- 
tablishment deny the existence of atypical presentations of Lyme, 
as some of those you have heard today, and the patients in this cat- 
egory are not being diagnosed or treated and have no place to go 
for proper care. 

The result of all this is that some Lyme patients have had to see. 
in my experience, as many as 42 different physicians over several 
years before being properly diagnosed, and also at tremendous cost 
to themselves. 

Unfortunately, the disease was left to progress during that time, 
and these patients were left forever ill, for by that time the illness 
was not able to be cured. 

Under the second category of undertreatment, number one is be- 
cause the diagnosis is not being made properly in many patients. 
Second, university-based and Government-endorsed treatment pro- 
tocols are empiric, insufficient, refer to studies involving inad- 
equate animal models, and are ignorant of basic pharmacology. 
They are not based on honest, systematic studies or on the results 
of newer information. 

Third, after short courses of treatment, patients with advanced 
disease rarely return to normal, yet many can be proven to still be 
infected and can often respond to further antibiotic therapy. Unfor- 
tunately, Lyme patients are being denied such therapy for political 
reasons and/or because insurance companies refuse to pay for these 
longer treatments. 

Fourth, long-term studies on patients who are undertreated or 
untreated demonstrated the occurrence of severe illness more than 
a decade later, reminiscent of the findings of the notorious 
Tuskegee Study. We have to take this illness seriously. 

Senator Wellstone. Dr. Burrascano, I don't want to be rude, but 
we're going to ask all of you to try to keep within about a 5-minute 
time frame. 

Dr. Burrascano. I am on the last paragraph. 

Senator Wellstone. OK I apologize. We just want to make sure 
that everybody has a chance to testify. 

Dr. Burrascano. I understand. 

Finally, the Lyme disease bacterium spreads to areas of the body 
that render this organism resistant to being killed by the immune 
system and by antibiotics, such as in the eye, deep within tendons, 
and within cells. The Lyme bacterium also has a very complex life 
cycle that renders is resistance to simple treatment strategies. 
Therefore, to be effective, antibiotics must be given in generous 
doses over a long period of time, sometimes many months, until 
signs of active infection have cleared. Also, because relapses have 
appeared very late, decades of follow-up are required before you 
can say someone has been adequately treated. 

I have to close by saying the very existence of hundreds of Lyme 
support groups in this country, and the tens of thousands of dissat- 
isfied, mistreated, and ill patients whom these groups represent, 
underscores the many problems that exist out in the real world of 
Lyme disease. I ask and plead with the committee to hear their 
voices, listen to their stories, and work in an honest and unbiased 
way to help and protect the many Americans whose health is at 
risk from what has now become a political disease. 

Thank you. 

----------

Comments:

It's 2011. This testimony was given in 1993. That's 18 years ago. 18. 

What has changed since this testimony was given?

I think most Lyme disease patients with persistent symptoms can relate to the statements made by Dr. Burrascano, and the echoes of what he said there have become part of the history and undercurrent for patients in discussions about insurance not covering their treatment and their ire about the IDSA Lyme disease treatment guidelines.

In discussion with a few people who were infected with Lyme disease many many years ago, I heard their uncommonly held opinion that this statement by Dr. Burrascano was perceived by them as a poor move on his part - even if some of the statements said were true. In doing so, he had raised the gauntlet and his open criticism before the Senate led to a backlash from different quarters.

As an aside, I'd really like someone to confirm if what I've heard about the time before his testimony was true: Prior to Burrascano's speech, some insurance companies were paying in full for IV antibiotic treatment for some patients. It wasn't a consistent practice - but in some places patients were able to get many months of IV antibiotic treatment covered by insurance. Insurance companies trusted the doctor's individual judgment for those cases.

Today, it is almost unheard of that an insurance company will cover any IV antibiotics for Lyme disease - if one receives 30 days' worth as a patient, they are lucky. It's almost as it neuroborreliosis doesn't happen, but it can and does happen earlier than one might suspect, given the stages of Lyme disease of which many people are familiar - and IV antibiotics is what neuroborreliosis requires.

Regarding the reaction to Burrascano's testimony, according to the LDF - there was retaliation - though I do not know the full story nor do I have independent confirmation of it.  What I do know is that to this day, there is a history of ongoing investigation into doctors who treat Lyme disease with long-term antibiotics - either by insurance companies, state medical boards, or both.

How this got started and who was the first doctor to do it is something I'd like to know - it had to be someone before Burrascano.

I look at all of this and what I hear in the Lyme patient community today springs forth from this event, and before this, the LDF, and before this, the Polly Murray story. I wonder how things came to be as they are - and inexplicably, why it is they haven't changed more in 18 years.

And interesting to note some of the other testimony by others that day... Sure, many people are familiar with the difference of opinion exchanged between Burrascano and Steere later that session, but how many are familiar with statements made by other researchers and doctors that day?

In my next post, part 2, I'll be pulling some of the more interesting passages out of the testimony for examination.

Note: For those of you who are concerned about my being plagued by virus yet still posting anyway when I said the frequency would slow down - I'm not great but okay. Most of what I'm writing here is copy and paste and not requiring much brain power... So I can post then lie down. - CO

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