I'm not much of a joiner. The only organizations I have ever joined - this suggests reference to the famous Groucho Marx joke - are the Democratic Party and the American Chemical Society. Recently I was solicited to join a group here of all places - one of those new fangled "groups" that go with the new structure of this website - by a Ms.Grin, who asked me to join the Lyme Disease Awareness group. She seemed so nice that I agreed to join and to write a diary on the subject of Lyme Disease pharmacology during Lyme Awareness Month, which I believe, is now.
This is that diary, although, it is probably not going to end up being about pharmacology per se, though I might suggest new molecular targets for the treatment of this widespread and debilitating disease, which is not to say that someone somewhere hasn't already thought of everything I suggest about molecular targets. (I would say that 90% of the ideas that seem to occur to me spontaneously seem to prove - upon investigation - to have been thought of by someone else and often by many people, which is to say many of my ideas are obvious.) I have no comprehensive knowledge of Lyme research; I have not been to medical school; and am - scientifically at least - merely a Lyme dilettante. As it happens, Lyme disease is not one of the diseases on which I have worked professionally, and I am certainly not qualified or competent to make definitive statements about Lyme.
That said, I have had this disease twice, once before being vaccinated, and once after being vaccinated. I received the (partially, obviously) effective vaccine for the disease before it was pulled from the market because of the risk of lawsuits.
One of my wife's relatives was one of the first people to be formally diagnosed with the disease: She is said to have lost her job (as a teacher) and, quite possibly, her husband as a result of the disease's complications. That's very serious, and very sad, since my wife's relative seems like such a nice person.
I am decidedly not a nice person, but I do have immediate access to the vast majority of the world's scientific literature - which I read incessantly - and feel I can (in a dilettante way) discuss the scientific issues and debates around Lyme disease, including the scientific community's reaction to the economic and political failure of the vaccine which, although it failed for me, had nothing to do at all with either its safety or its effectiveness.
This is one strange country we live in.
One more thing about me, by way of full disclosure: When I set out to do library research on this disease a few Saturdays ago, I took my sons with me, as part of our new "Saturday homework in a university library" scheme. On the way over - it almost seems like karma - my oldest asked me, "Dad, what's a nihilist?"
"Your dad," I answered.
I should have answered - but didn't - that nihilism is a symptom of poorly treated - or ineffectively treated - persistent idealism.
My boy seems like such a nice boy, though, and whether I am a nihilist or not, I love him a great deal and worry all the time - given his long hair which he refuses to cut - that he will get Lyme disease and be permanently injured like his relative. Even as a nice boy, like all humanity he faces enormous risks merely as the result of the pleasure and the terror of being alive, and there's no way he needs the burden at his age in understanding nihilism or, for that matter, solipsism, or any other thing dribbling out of the mouth of a cynical and dispirited old man who will decidedly not live to be 104.. (Thanks be to Allah, or one of those other supernatural omniscient beings.) When I say that I will not live to be 104, although I'm younger maybe than some people who think they will, I am not by the way, soothsaying.
Soothsaying is for mystics. Facing facts, maybe, is not.
As for my son, and the world I gave him and any need I might have to educate him about nihilism: Fuggetaboutit. If he can be young, I should let him do so!
Whether or not my answer to the earnest question, "What is a nihilist?" was intended for a laugh, or for something else, one may consider whether this is a nihilist Lyme diary - for whatever it's worth and thus take it with a grain - or large carefully grown large ordered crystal - of salt and recognize that it is not intended to be definitive. No one should take medical advice from a blog, even a doctor's blog like the one I'll reference below.
Science blogging is almost certainly a very, very, very, very bad idea.
Enough with disclaimers, about Lyme disease:
May is Lyme Disease Awareness Month
Lyme is the most prevalent vector-borne disease and one of the fastest spreading diseases throughout the United States, and the subjects of diagnosis and treatment of Lyme are politically-charged.
This series of diaries is designed to provide information to the Daily Kos community both for Lyme disease prevention and for those Kossacks living with Lyme. Because the disease is often missed by physicians, these diaries may assist an individual or two in pursuing testing which might otherwise have been missed.
The Lyme Disease Awareness series is eclectic, including personal statements, informational pieces about the science of Lyme, and calls to action for community and political advocacy.
We hope you'll all join us all month in learning about this rampant disease and the medical/financial/political morass in which Lyme patients find themselves.
Whether or not you are a member of this group, it appears you will need to FOLLOW in order to have the diaries show up in your stream. We invite you to join and follow us.
Lyme disease as a huge public health problem is relatively new, although it is likely that the disease and the organism responsible for it, Borrelia burgdorferi have been around for a long time. Borrelia burgdorferi is a resident of spirochete phylum which interestingly, was one of the few phyla to have been correctly identified on taxonomic morphological properties alone, which is to say that the morphological classification was confirmed by analysis of its genome.
To wit:
Spirochetes are one of the few groupings correctly identified by classical (morphological) criteria (167). Their common spiral shape and axially coiled fibrils, lying between inner and outer cell envelopes, are strikingly characteristic (24). Table 11 shows representative species whose rRNAs have been characterized, in rough phylogenetic arrangement. The sequence signature for the group shown in Table 3 is quite distinctive. For example, the U residue at position 47 found in all species from this group occurs nowhere else among eubacteria (266; unpublished analysis).
(Ref: Woerse, MICROBIOLOGICAL REVIEWS, June 1987, p. 221-271, quote from page 243)
The complete genome of the Borrelia burgdorferi organism has been fully sequenced (cf. Nature 390, 580–586, 1997) and is found to consist of a linear chromosome of 910,725 base pairs and 17 plasmids linear and circular plasmids, containing about 533,000 base pairs. The Nature article indicates that there are 10 species of Borrelia.
Plasmids are (usually) short sequences of DNA that reside in certain cells and reproduce independently of the main chromosomes.
Generally plasmids are not considered to be common in eukaryotic cells - although one might reasonably argue that certain organelles in the cells of so called "higher organisms" including human beings and American Chestnut trees such as mitochondria and chloroplasts are in fact plasmids contained within membranes - but are widely found in bacteria like Borellia species. Possibly this is a result of bacterial conjugation, and may also be associated with bacteriophages, which are viruses that infect bacteria. (As it happens, one of the huge surprises of the famed somewhat overly hyped human genome project was the discovery that huge sections of the human genome consists of viral DNA, much of which is useless and carried along as baggage, but some of which is functional.) Sometimes DNA particles that are not defined formally as plasmids can be found in higher organisms as a result of damage from things like the radiation that recently killed everyone in Japan, or other sources of radical forming physical biochemistry, stuff like, um, smoke. In this case, the DNA strands are not called "plasmids" usually, but are referred to as microsatellites. It is known that the voles - voles are rodents - living in the forests around the Chernobyl reactor that wiped out Ukraine have elevated levels of microsatellites in their DNA. The physiological effects of the presence of microsatellites in animals like voles are not well understood, but it is clear that the voles, while they might not live to be 104, can live with some cells containing microsatellites. What are more problematic probably are microsatellites in germ cells, but one might reasonably argue that DNA disruptions in germ cells are a normal - and necessary - feature of evolution itself.
One cannot believe in evolution, by the way. One can either understand it, or deny it, although the popular practice of denial has nothing to do with physical outcomes in the universe. (The statement about denial in science should hardly be limited to discussions of evolution, by the way.)
Voles, as it turns out, are of interest in the evolution of Borrelia species. It is very, very, very, very difficult to culture Borrelia species in the laboratory. One of the reasons for this is that Borrelia species have generally evolved very specific host/parasite relationships and some can only infect certain species of mammals and ticks and don't just grow anywhere. Because of this specificity, it is difficult to constitute the correct growth media. The upside of course is that Lyme disease is not, absent ticks, contagious. There is a species of Borellia that is confined to voles. The Lyme parasite, Borrelia burgdorferi is somewhat unique in this regard: It is not confined to just one species of mammal although it is confined to a single genus of tick, Ixodid genera. In the United States the most common species of tick for the transmission of Lyme disease is Ixodid scapularis. I will say some more about some interesting molecular biology associated with ticks later.
More modern papers indicate that there are 12 species, not 10, four of which. including the aforementioned Borrelia burgdorferi, are pathogenic. Borrelia garinii, Borrelia afzelii and Borrelia spielmanii, are also pathogenic. The pathogenic species all exhibit tissue tropism, meaning they migrate toward specific tissues where they cause disease. Eight species of Borrelia are believed to be relatively benign, although two are potentially pathogenic. (cf. International Journal of Medical Microbiology 297 (2007) 263–271).
Borrelia ganrinii is primarily found in Europe.
Borrelia afzelii is found in Japan, or was, until Japan was completely wiped out not from an earthquake or a tsunami, but from massive radiation sickness, as I have learned from reading here, and in the New York Times. Whether the mass extinction of Japanese has negated the problem with Japanese Lyme - formerly found largely in the Northern regions - is not for me to say.
Anyway.
Borrelia burgdorferi is a flagellate motile bacterium, and an interesting fact is that its flagella proteins show a high degree of homology with other pathogenic bacteria, specifically Salmonella typhimurium,(St), Escherichia coli (EC) and Bacillus subtilis (Bs). (cf.Gene. 168 (1996) 73-75). This suggests ancient common ancestry for these very different disease causing bacteria.
The highly conserved flagellate proteins however may have nothing to do with the fact that all of these bacteria are pathogens. As it happens, I have read a great deal about Lyme disease in the last few weeks, and one of the papers I recall reading - but cannot cite without wading through the mass all over again - indicated that the pathogenic properties of Lyme are not associated with the linear main chromosomes, but are in fact associated with plasmid DNA.
Borrelia species and Lyme disease are thought by many to be limited to the Eastern United States, however Borrelia burgdorferi is known in Europe, and in fact, through much of North America. In Europe the most common tick for transmission is Ixodes ricinus. This suggests that the disease has been around for a long time, but probably has missed diagnosis until recent times. Like other diseases, notably AIDS - about which I happen to know more than I do about than I do about Lyme disease, although I have had the latter and am very, very, very low risk for the former - it is probable that the high infection rates observed in modern times are involved with the penetration of humans into previously sparsely populated regions, coupled with some mutagenesis. An alternative explanation is of course that the disease has been spread by the high mobility of the Homo sapiens organism.
As I mentioned above with some of my trademark sarcasm, Lyme disease is also known (or was known) in Japan. Before Fukushima killed everyone in Japan - an issue that seems to have been displaced in the pages of our wonderful scientifically literate press in this country by the death of some Arab guy with a name that sort of sounds like our President's name, one guy, in Pakistan - the ticks that transported lyme in Japan were Ixodes tanuki, I. turdus, and I. columnae. (cf. FEMS Microbiology Letters 142 (1996) 77-83)
Ixodes turdus?
This said, it is clear that there are still - or were as of 15 years ago - geographically distinct populations of not only of the Borrelia genus, but also within the Borrelia burgdorferi species as a whole. Strains isolated from places as different as Shelter Island, New York - which is geographically isolated - as well as West Chester County, New York (Milbrook); Marshfield, Wisconsin; and Del Norte, California - all isolated from Ixodid ticks, with the California version coming from the I. Pacifica species as opposed to the I. scapularis species, were analyzed for homology with the 23 S ribosomal DNA molecule that is responsible for protein synthesis in the Borrelia organism, showed broad polymorphism in this protein. (cf. Res. Microbiol. 1995, 146, 415-424). The authors of the paper just cited noted that there are significant differences in European Lyme as opposed to the US version, with the European strains exhibiting far more neurological symptoms. (By contrast, studies of the 16S ribosomal DNA showed highly conserved nucleotide sequences in widely distributed strains.)
To wit:
The extensive antigenic and genetic diversity demonstrated among isolates of B. burgdorferi sensu lato is commensurate with the wide variety of disease manifestations attributed to infection with this spirochete (reviewed by Steere, 1989).
It has been suggested that Lyme disease in Europe may result in severe neurologic abnormalities, in contrast to disease in the United States, in which a milder form of neuroborreliosis and arthritis are more frequent findings (Halpetin, 1991).
I am not qualified to adjudge whether any specifics about symptomology associated with Lyme disease derive from specific strains, and indeed I am not qualified to say anything at all about the diagnosis of Lyme. I will say this: My former doctor misdiagnosed my second bout with Lyme disease, thinking I had H1N1. Happily for me - I was about to go on a business trip to California - I observed (actually my wife observed) a classic bulls eye rash from the disease and I went back to my doctor who cheerfully corrected my diagnosis and treatment course.
This is not why he is my former doctor, by the way. He recently sold his practice - despairing of true health care reform - to a corporation, specifically Proctor and Gamble - which is buying up medical practices in a new scheme called MDVIP, which requires patients to pay a retainer to retain access to their physicians. I liked my doctor, and considered him a friend for 18 years, but my wife and I reasonably agreed that there was no way we could fork over $3,000 bucks a year as a retainer for the two of us. I respect his decision, and understand it on some level, and could not fault his patient explanation of why he was doing that, selling his practice, and his feeling of pain about it, but, it is what it is.
Patients should be aware of health issues, but they should not assume that they always or even often know more than their physicians do. Even among people who have been to medical school the saying exists that a physician who treats himself has a fool for a patient.
I am aware of some very disturbing cases in this area as a result of my library research.
I will have something more to say about that in a future installment in this diary series, unless the group leader emails me to ask me not to write more diaries.
The working title for that installment is "The Lymerix Vaccine and the Mob!" In that one I'll discuss blogging doctors, and the issue of the neurological effects - putative and otherwise - of Lyme disease.
Another part of this series, might be about the interesting molecular biology of ticks and their interaction with the immune system of hosts. Should I write that diary, I will discuss a species of tick that actually is toxic to Borrelia species, and therein suggest a new molecular target.
But it's, um, Sunday night, and I have so much going on and Ms.Grin may have dispaired of me ever writing a promised diary, so I'll take a break here.