Friday, March 31, 2006

31st meeting of the skeptics circle

Abel Pharmboy at Terra Sigillata has hosted one of the biggest skeptics circles I've seen in a while. There is a plethora of skeptical entries this week on a wide range of topics so it's well worth the visit. The next circle is being hosted by our very own pooflinger at Pooflingers Anonymous so presumably check over there for contact details.

Thursday, March 30, 2006

What evidence suggests badgers infect cattle with M. bovis?

Part III: Mycobacterium bovis, the English bovine tuberculosis outbreak, badgers and the culling debate.

Critical to the entire culling controversy as a control measure for M. bovis is what the exact role of the Eurasian badger (Meles meles) in the spread of bovine tuberculosis. If badgers are the principal source of bovine tuberculosis, then a cull would make sense and would have the maximum effect on reducing breakdowns (a case of bovine tuberculosis in a cattle herd). If badgers are not the principal source of bovine tuberculosis, or alternatively they are but cannot spread bovine tuberculosis to cattle, then a cull is just going to be a needless waste of time with ultimately no effect as several conservationists have argued. So what does the scientific literature actually say?

Are badgers actually infected with bovine tuberculosis and if so, can they secrete Mycobacterium bovis?

One of the most recent studies relevant to this question is from Chambers et al., (2002) and investigated the current serological tests for identifying badgers that shed Mycobacterium bovis. This study compared two methods, notably ELISA (Enzyme Linked ImmunoSorbent Assay) and Western blotting against direct culture of M. bovis for accurately identifying infected badgers. Importantly, this study was set up to determine if these techniques could accurately determine if a badger was secreting M. bovis. Essentially, the scientists picked an area that had endemic infection with M. bovis among cattle herds and captured 128 badgers. Of these sampled badgers, 44 were confirmed to have secreted M. bovis at some point in their life as confirmed by the ELISA, Western blot and culture detection methods.

With the use of all three methods concordantly it makes it virtually impossible that the result is incorrect or outside factors such as other environmental mycobacteria (Primm et al., 2004) are responsible and as such, the study clearly implicates badgers as a host for M. bovis. Of course, science does not stand simply by itself but rather through the work that others have done in the past and what studies have followed afterwards. Here the consensus is overwhelming. For instance, a previous study from Gallagher and Clifton Hadley (2000) shows that badgers had M. bovis infection in both lung tissue and in their urine from post-mortem examination. Other studies from Costello et al., (1999) and Olea-Popelka et al., (2005) have found that badgers are infected with M. bovis and most importantly, the same strains of M. bovis tend to be shared between cattle and badgers in the same area (this is an important point, more on this later however).

Further, the two key ‘trials’ conducted on the effects of badger culling by Donnelly et al., (2002, 2006) in England and the “Four counties” trial in Ireland by Griffin et al., (2005). Both of these studies have found that bovine tuberculosis is present among badgers around farming areas. Typical prevalence of infected badgers tends to fluctuate widely, with some researchers finding infection rates around 20% and others up to 50% (Corner L.A.L., 2006). In short, numerous studies have all universally been able to find badgers that have been infected with M. bovis. The question remains as to if infected badgers secrete M. bovis that can infect cattle?

In order to spread efficiently from badgers to cattle it’s important to realize that several factors need to occur for any chance of transmission:

1) Badgers need to come into contact with cattle or alternatively, cattle come into contact with feces and other excretions of badgers.

2) Infected badgers must be able to secrete M. bovis to cattle through excretions such as sputum and urine.

3) M. bovis in badger excretions must have some mechanism to survive the passage from a badger to cattle.

We should also expect if these three things are found and that if badgers are transmitting M. bovis to cattle (somehow), then we’d also expect to see the same spoligotypes in cattle and local badgers. So once again, what does the literature say on these three issues?

Possible means of transmission of cattle to badgers.

Several studies have identified that badgers are not afraid to come into contact with cattle, although the circumstances in which badgers come into contact differ. Phillips et al., (2003) and Corner L.A.L. (2006), both report that cattle will typically avoid badgers if at all possible. Interestingly, both papers note that heavily infected badgers tend to behave aberrantly and that cattle will frequently investigate by licking, sniffing and biting. This matches similar observations of cattle in New Zealand investigating brushtail possums that are dying of TB.

Additionally cattle are also highly likely to come into contact with the excretions of badgers such as urine, feces and sputum. As badgers excrete copious amounts of infectious bacteria in their sputum (coughed up fluid), urine and from infected bite wounds this does pose a possible risk for cattle grazing in fields visited by badgers (Krebs et al., 1998; Phillips et al., 2003; Scantlebury et al., 2004 and Young et al., 2005). Additionally, badgers are also capable of surviving with tuberculosis for months or even years and may be infectious for long periods of time, until they eventually succumb to infection (Phillips et al., 2003; Scantlebury et al., 2004 and Corner L.A.L., 2006).

Finally, it is also the case that cattle will graze areas that have been used as latrines or ‘crossing points’, essentially places badgers tend to go over often when moving from field to field, which poses a potential risk of ingesting M. bovis. Interestingly the main means of infection in cattle is from aerosolized particles and not from ingestion. This is supported by the fact infected lesions and bacteria from infected cattle are typically isolated from around the head region more so than GALT* (Phillips et al., 2003).

Scantlebury et al., (2004) noted that intensively farmed cattle tended to graze badger latrines and crossing points immediately due to sward (grass) competition. Conversely, cattle farmed in less dense numbers tended to scratch and sniff latrines or badger urine (crossing points) but ultimately avoid these areas. Rates and reasons for cattle investigation or consummation of swards infected with badger excretions should deserve further analysis.

Finally M. bovis is more than capable of surviving outside of the host once it has been excreted. As mentioned in part II, mycobacteria are particularly hardy organisms and have a wide metabolism. M. bovis in soil samples has been demonstrated to be viable for months by culture and may even be viable for years (Young et al., 2005). This is because although previous studies that have failed to culture M. bovis after long periods of time, molecular methods for the detection of RNA have indicated the organism could still be present but non-culturable (Young et al., 2005). In a similar manner to other microbes, it is possible for a viable organism to exist in the environment that cannot be cultured for whatever reason (Colwell and Grimes, 2000).

The final link in the chain.

Generally infected badgers tend to be found in clusters, with the surrounding cattle farms also infected with the same strains of M. bovis (Costello et al., 1999; Smith et al., 2003; Griffin et al., 2005 and Olea-Popelka et al., 2005, 2006). Additionally, many studies have indicated that badgers may roam relatively widely and have varying levels of contact with cattle, see for examples Griffin et al., 2005 and Olea-Popelka et al., 2006. As mentioned earlier, this concordance between the general spoligotypes in an area being the same between those found in infected cattle and nearby infected badger setts resolves the issue. It’s almost certain that badgers are to some degree responsible for spreading M. bovis to cattle, even if the exact mechanism is unknown and has yet to be illucidated (Olea-Popelka et al., 2006).

It’s very clear that badgers can be infected by M. bovis, excrete the organism in their sputum and urine due to chronic infection of the lungs and kidneys and that the same strains of M. bovis that infect badgers are found in cattle. Also importantly, the proactive culling portions of the Donnelly et al., (2003, 2006) study and the Griffin et al., (2005) “four counties” trial have shown considerable drops in the prevalence of herd breakdowns**. Finally however, if you’re the sort of person who requires a more ‘visual’ aid, then I would propose having a look at this poor badger (Horrific image! Do NOT click it unless you like copious amounts of pus!), which has died of tuberculosis and believe me, it’s not a pretty sight.

However, despite the strength of the evidence presented from the literature supporting a link between badgers and bovine tuberculosis, it’s insufficient to resolve the issue mentioned in the opening paragraph. Even if badgers are responsible for spreading tuberculosis, the role of cattle will also need to be determined as it may be possible that badgers are only a symptom, and not the cause of the high prevalence of BTB in the UK. Keep checking back soon for this question to be addressed in Part IV: The role of cattle movements in the bovine TB epidemic.

*GALT=Gastrointestinal Associated Lymphoid Tissue.

**I will point out before someone else does, that I’m aware the reactive culling part of the Donnelly studies have shown an increase in herd breakdowns. I’m not deliberately ignoring this point as I intend to cover this later in the series.

References

Chambers M.A., W.A. Pressling, C.L. Cheeseman, R.S. Clifton-Hadley and R.G. Hewinson (2002). Value of existing serological tests for identifying badgers that shed Mycobacterium bovis. Veterinary Microbiology, 86:183-189.

Colwell R.R. and Grimes D.J. (2000). Nonculturable microorganisms in the environment. ASM press Washington D.C.

Corner L.A.L. (2006). The role of wild animal populations in the epidemiology of tuberculosis in domestic animals: How to assess the risk. Veterinary microbiology, 112:303-312.

Costello E., D. O’Grady, O. Flynn, R. O’Brien, M. Rogers, F. Quigly, J. Egan and J. Griffin (1999). Study of restriction fragment length polymorphism analysis and spoliogotyping for epidemiological investigation of Mycobacterium bovis infection. The Journal of Clinical Microbiology, 37:3217-3222.

Donnelly C.A., R. Woodroffe, D.R. Cox, J. Bourne, G. Gettinby, A.M. Le Fevre, J.P. McInerney and W.I. Morrison (2003). Impact of localized badger culling on tuberculosis incidence in British cattle. Nature, 426:834-837.

Donnelly C.A., R. Woodroffe, D.R. Cox, F.J. Bourne, C.L. Cheeseman, R.S. Clifton-Hadley, G. Wei, G. Gettinby, P. Gilks, H. Jenkins, W.T. Johnston, A.M. Le Fevre, J.P. McInerney and W.I. Morrison (2006). Positive and negative effects of widespread badger culling on tuberculosis in cattle. Nature, 439:843-846.

Gallagher J. and R.S. Clifton Hadley (2000). Tuberculosis in badgers: a review of the disease and its significance for other animals. Research in Veterinary Science, 69:203-207.

Griffin J.M., D.H. Williams, G.E. Kelly, T.A. Clegg, I. O’Boyle, J.D. Collins and S.J. More (2005). The impact of badger removal on the control of tuberculosis in cattle herds in Ireland. Preventative Veterinary Medicine, 67:237-266.

Krebs J.R., R.M. Anderson, T. Clutton-Brock, C.A. Donnelly, S. Frost, W.I. Morrison, R. Woodroffe and D. Young (1998). Badgers and bovine TB: Conflicts between conservation and health. Science, 279:817-818.

Olea-Popelka F.J., O. Flynn, E. Costello, G. McGrath, J.D. Collings, J. O’Keeffe, D.F. Kelton, O. Berke and S.W. Marin (2005). Spatial relationship between Mycobacterium bovis strains in cattle and badgers in four areas in Ireland. Preventative Veterinary Medicine, 71:57-70.

Olea-Popelka F.J., J. Phelan, P.W. White, G. McGrath, J.D. Collins, J. O’Keeffe, M. Duggan, D.M. Collins, D.F. Kelton, O. Berke, S.J. More and S.W. Martin (2006). Quantifying badger exposure and the risk of bovine tuberculosis for cattle herds in county Kilkenny, Ireland. Preventative Veterinary Medicine, epub ahead of print.

Phillips C.J.C., C.R.W. Foster, P.A. Morris and R. Teverson (2003).The transmission of Mycobacterium bovis infection to cattle. Research in Veterinary Science, 74:1-15.

Primm P., C.A. Lucero and J.O. Falkinham III (2004). Health Impacts of Environmental Mycobacteria. Clinical Microbiology Reviews, 17:1,98–106.

Scantlebury M., M.R. Hutchings, D.J. Allcroft and S. Harris (2004). Risk of disease from wildlife reservoirs: Badgers, cattle and bovine tuberculosis. Journal of Dairy Science, 87:330-339.

Smith N.H., J. Dale, J. Inwald, S. Palmer, S.V. Gordon, R.G. Hewinson and J.M. Smith (2003). The population structure of Mycobacterium bovis in Great Britain: Clonal expansion. PNAS, 100:15271-15275.

Young J.S., E. Gormley and E.M.H. Wellington (2005). Molecular detection of Mycobacterium bovis and Mycobacterium bovis BCG in soil. Applied and Environmental Microbiology, 1946-1952.

V for Vendetta

I just came back from this movie and all I can say is that it's politically heavy handed but overall it's a very good film. There are some things that don't make much sense and sometimes the movie is all over the place, but is overall far from the boredom that the Matrix sequels ended up being. It's definitely worth seeing.

Wednesday, March 29, 2006

PNAS cover this week

This weeks cover photo for the Proceedings of the National Academy of Sciences (PNAS) is really nice. The photo is of some rat alveolar macrophages taken from the lungs of rats taking up some polystyrene disk particles. I think it's a very pretty looking photo and demonstrates the wonderful function macrophages have in being the 'clean up' crew of the body. The photos accreditation is to Julie A. Champion who is the author of an interesting paper published in that issue of PNAS, which is looking at how particle size and shape affects the uptake of particles by macrophages.

Image hosting by Photobucket

Wonderful photo. As a side note, I would suspect the sample was prepared for a scanning electron microscope and then the subsequent captured image above has been 'colourised' (just like Ted Turner!) by a computer. Normally images that you see through electron microscopes aren't very pretty and are pretty much just all grey.

How evil am I?

You Are 24% Evil

A bit of evil lurks in your heart, but you hide it well.
In some ways, you are the most dangerous kind of evil.

A bit disappointing really. It seems that I've fallen well behind in being corrupted by anime, blaming my flatulence on others and evilution. I need to try harder it seems.

Chick tract on chemicals

Jack Chick likes to write comics that tend to generally convey his anger about certain issues or things he finds offensive: just about anything in other words. One of his older comics was on a group of people playing DnD and was basically a huge strawman. I won't directly link it, because Jack Chick deserves no extra bandwidth in general and out of consideration for the mental health and stability of my readers. It is good then that Bronze Dog from Rockstars' Ramblings has come up with a highly amusing 'edit' of the original Jack Chicks comic. It certainly has inspired me to try an "argument ad baculum" on anyone who disagrees with me.

Tuesday, March 28, 2006

Awesome giant centipede video

I saw this video over at pharyngula and concluded it was too awesome not to provide yet another link to. Essentially this is a video of a >1 foot long giant centipede (Scolopendra) attacking, killing and then devouring a mouse. There is only a few seconds of squeaking after the first strike and then the copious amounts of poison that the animal secretes through its maxillipeds (the part that bites the mouse). It's worth noting for those watching the video (probably with some horror) that the maxillipeds aren't what the centipede uses to eat the mouse. These structures are adapted to secrete venom and additionally kill by impalation (a favoured tactic of other large arthropods like tarantulas as well), but they do have mandibles and if you watch the head closely, you can observe the centipede chewing away on the mouse with its mandibles (under the head).

Centipedes are very underrated killers of the arthropod world. This is obviously the start of an effective (and equally horrible) PR campaign.

Update: I missed it the first time, but also note the spots of liquid that suddenly appear between the joints of the centipedes body as it wrestles with the mouse. I would guess that's actually even more venom, although I've normally only heard of centipedes releasing venom from between their leg joints and not their main segments. That's a pretty awesome adaptation if they can secrete venom that way as well though. It's not entirely without precedent though, the centipedes close relatives milipedes are known to secrete cyanide and other toxic compounds from their joints when harassed.

Monday, March 27, 2006

Plush Kiwa Hirsuta

Remember that furry crustacean that everyone was oogling over from a while back? Well it looks like the obvious thing to do, which would be to make a plush toy of it has now officially occured. I think the toy version looks great and I would most definitely buy one if I ever got the opportunity.

How much does my blog own me?

I noticed that several sciencebloggers did this amusing little test to determine how much their blogs own them. Apparently, this site owns 31.25% of me or something like that. At least it's not a majority share, which I would like to think my passion of science or my obsession with spiders would own the rest of me easily. They can battle it out.

Oh the Onion

I love the Onion, which is so good at satire that sometimes people mistake articles from it for the real thing. Usually they manage to hit home on various points or just make a particularly funny joke. The latest edition has the following 'brief' about a chicken interviewed about having Bird Flu:
DILLON, SC—A chicken at Perdue Farms' Dillon plant downplayed reports of illness Tuesday, saying she was feeling much better. "I might have had a touch of some sort of flu, but I'm over my fever and keeping the ol' corn down. B'cawk!"
I suspect that the chicken wouldn't have even got past the first few sniffles with the current climate about bird flu. Speaking of bird flu now I think of it, if you haven't been to Effect Measure lately and read their excellent summary of two papers about bird flu and where it potentially binds onto human lung tissue, I would very much recommend doing so. It's very well written and much better reasoned than the mainstream news reports, which seem to always miss the key points.

Sunday, March 26, 2006

What makes Mycobacterium bovis such a problem?

Part II: Mycobacterium bovis, the English bovine tuberculosis outbreak, badgers and the culling debate.

Mycobacteria represent a large group of incredibly tough environmental bacteria that have in many cases adapted to be successful pathogens, which are classically very slow in killing their victims. One such mycobacterial disease is tuberculosis, caused by Mycobacterium tuberculosis, which is probably one of the oldest described diseases known to man. The hardy organisms have been found to be responsible for the deaths of Egyptian Pharaohs and the disease was often described as “White plague” in the middle ages. This was because heavily infected victims cough up an off white frothy substance, packed with M. tuberculosis and blood, called sputum. M. tuberculosis is remarkable in another way; as one of the most significant diseases humans passed to animals (rather than vice versa), in this case to cattle some 6 to 10 thousand years ago. The product of that jump over the species barrier was Mycobacterium bovis, which is today one of the most prevalent and significant pathogens of domestic and wild animals.

Why mycobacteria are such good pathogens

Mycobacteria represent an ultimate trade off between factors that make them highly difficult to kill for the host immune system and yet heavily restrict their own growth. This means that mycobacterial diseases are classically slow taking months or years to cause disease, are usually very debilitating and go completely undetected until it’s too late. Arguably the most important factor for the success of mycobacteria such as M. bovis as a pathogen is their amazingly tough cell wall.

Unlike other bacteria, the cell walls of mycobacteria are heavily composed of lipids that make them extremely tough. This tough wall makes it very difficult for cells of the immune system, like macrophages to break down the organism and M. bovis will survive quite well in microphages. Despite the advantage of higher protection such an unusual cell wall does come with some key trade offs. Their cell wall is not very permeable to many substances, giving the microbe a tougher time acquiring nutrients and the organism spends large amounts of energy synthesizing fatty acids.

Another unusual characteristic of mycobacteria is that they have only one or two 16S ribosomal RNA cistrons (compared to 7 in Escherichia coli). This contributes to the immensely slow growth of mycobacteria as ribosomes are essential in the rapid production of new proteins, so the inability to rapidly produce more ribosomes means the microbes maximum growth speed is pretty much capped. Comparing E. coli to M. bovis is rather like comparing a Ferrari with a broken down jalopy with one wheel missing.

It can take (for example) up to two weeks to grow mycobacteria to useful numbers for an experiment in a lab, compared to one day for E. coli. Although seemingly a stupid idea for the organisms survival initially, it does have two key advantages. It’s very useful against antibiotics that target the ribosome, as only one mutation can instantly make the organism resistant and prevent any real damage. Additionally a slow growth rate makes it very easy to assess a changing situation and adapt to the new situation without committing to an ‘all or nothing’ style scenario.

Finally, mycobacteria are easily aerosolized (so they spread between individuals easily), are taken up by macrophages rapidly and are fairly drug resistant (largely due to their cell wall and their slow metabolism). Worst of all, the large presence of environmental reservoirs of mycobacteria makes an effective vaccination difficult. The current BCG vaccine (Bacillus of Calmette-Geurin) has often been found to be ineffective in providing immunological protection and part of the suspected reason for this is ‘confusion’ of the immune system by environmental mycobacteria.

M. bovis provides a particular threat to farm economies

Perhaps the most prominent reason for the problem with eliminating M. bovis from cattle is the large host range that M. bovis exhibits. As well as cattle and to a lesser extent humans the organism is known to infect badgers, possums, deer, sheep, ferrets, oxen, buffalo, lions and wildebeest. This immensely large host range makes control of the disease almost impossible in areas where there is a wild animal reservoir that can prevent elimination of M. bovis. The large host range of M. bovis is almost certainly a result of its wide metabolism and the fact most mammalian immune systems are pretty similar.

Elimination of this disease in some places of the world, such as New Zealand and the United Kingdom that has animal reservoirs is hence very difficult. Making things worse, the suspected animal reservoirs are also found in close association with cattle that are susceptible to infection. The important question that needs to be answered is what role do these vectors play in the transfer of M. bovis to cattle? Join us back this week for part III: What evidence suggests badgers infect cattle with M. bovis?

References

Primm P., C.A. Lucero and J.O. Falkinham III (2004). Health Impacts of Environmental Mycobacteria. Clinical Microbiology Reviews, 17:1,98–106.

Salyers A.A. and D.D. Whitt (2002). Bacterial Pathogenesis: A molecular approach 2nd edition. ASM press, Chapter 19:291-310.

Previous post by me about the origins of M. bovis. The quoted paper in particular.

Britannica upset with Nature

A while back, Nature posted a comparison of the free encyclopaedia wikipedia with that of the formal published Britannica. It appears that the general conclusion Nature reached, which was that wikipedia was sometimes as accurate or even better than Britannica on scientific articles has struck a nerve. Nature begin their response pointing out what they were accused of:
In our issue of 15 December 2005 we published a news article that compared the Internet offerings of Encyclopaedia Britannica and Wikipedia on scientific topics (“Internet encyclopaedias go head to head”, Nature 438 (7070) p900-901; http://dx.doi.org/10.1038/438900a). Encyclopaedia Britannica has now posted a lengthy response to this article on its website, accusing Nature of misrepresentation, sloppiness and indifference to scholarly standards, and calling on us to retract our article. We reject those accusations, and are confident our comparison was fair.
The original analysis didn't seem to have been flawed in any particular manner and seemed to have been perfectly fair, though I feel Britannica does have a few legitimate complaints in places. Firstly, Nature did only take smaller segments from articles to show their reviewers and often some of the complaints were addressed in the larger body of text. Additionally, Nature seems to have taken material that is from other editions of the encyclopaedia, which are intended for younger audiences or not included in the main edition of Britannica. I do see that as a valid complaint because that would skew the analysis. After-all Nature are implying the wiki gets as accurate as the encyclopaedia Britannica, which is a somewhat different thing than their other publications.

Otherwise, through reading both the responses from Nature and Britannica, it does seem that Britannica were trying to save face and their reputation primarily as many of their complaints, such as shortening articles, were equally applied to wiki articles by Nature. Of course this defensive response from Britannica does make sense, who would want to be beaten out by a free online encyclopaedia that's not even written by experts? This point in particular seems to have got Britannicas goat, as you can see here from the opening of Britannicas response:
In its December 15, 2005, issue, the science journal Nature published an article that claimed to compare the accuracy of the online Encyclopædia Britannica with Wikipedia, the Internet database that allows anyone, regardless of knowledge or qualifications, to write and edit articles on any subject.
Which then moves onto a typical attack that the wiki often hears from its detractors:
Wikipedia had recently received attention for its alleged inaccuracies, but Nature’s article claimed to have found that “such high-profile examples [of major errors in Wikipedia] are the exception rather than the rule” and that “the difference in accuracy [between Britannica and Wikipedia] was not particularly great.”

Arriving amid the revelations of vandalism and errors in Wikipedia, such a finding was, not surprisingly, big news. Within hours of the article’s appearance on Nature’s Web site, media organizations worldwide proclaimed that Wikipedia was almost as accurate as the oldest continuously published reference work in the English language.
This is often a problem with the wiki, particularly on controversial issues like evolution, the holocaust and other contentious articles that are prone to vandalism. Many of the articles on wikipedia are of a very high quality however and are well maintained by individuals with expertise in their fields. Unfortunately, the wiki seems better for "fan cruft" and other similar information like details about popular computer games or anime series than as a scholarly resource at the moment.

In any particular event, I think that Nature probably weren't as careful with their analysis as they could have been originally. Some of the mistakes that Nature claim to have identify in the Britannica articles do not appear to be overly relevant at times (see Britannicas response for some details). Without seeing what the same reviewers thought about the relevant wikipedia articles, it would be impossible to determine if there was any real reviewer bias either way. Hopefully Nature will produce a more detailed response that clarifies how their reviewers went about determining errors and the like. Importantly, I would like to know how Nature decided what parts of the articles to take as that could heavily impact on the end result.

Saturday, March 25, 2006

When public health, farm economics and conservation collide

Part I: Mycobacterium bovis, the English bovine tuberculosis outbreak, badgers and the culling debate.

One of the most prominent problems for public health authorities and a countries economy comes from infectious diseases that target farmed animals. There are a wide number of pathogens that affect the animals that we grow as food that present a real public health risk, such as Campylobacter jejuni in chickens, Escherichia coli O7H157 in cattle and mycobacteria like Mycobacterium avium subspecies paratuberculosis in sheep. Control of these organisms often involves improvements in animal husbandry, such as simple measures like keeping animals separated and the use of improved diagnostics or vaccinations. Where these control measures become insufficient is when the disease has other vectors, which are also in high numbers and present unique difficulties in controlling or eliminating. Such is the problem that several countries face in controlling bovine tuberculosis, caused by Mycobacterium bovis a relative of one of man-kinds earliest known pathogens, Mycobacterium tuberculosis.

M. bovis historically was a considerable risk to human health, as the organism is viable in milk and of course in the meat of infected cattle. An inquiry in 1934 determined that M. bovis was responsible for some 2,000 tuberculosis deaths (around 6% of the total, the rest being caused by the human specific M. tuberculosis). Today, M. bovis is not much of a problem in humans, as the introduction of milk pasteurization and particularly tuberculin testing has entirely eliminated bovine tuberculosis as a human and animal health threat. This is because tuberculin testing allows for the identification of animals potentially infected with M. bovis and their rapid slaughter and removal from the herd. This policy has completely eliminated M.bovis from cattle herds world wide, except in certain countries such as the United Kingdom (notably Wales, Ireland and England), New Zealand and the state of Michigan in the United States of America.

The question then has to be asked in what makes these regions so different from the rest of the world? The simple answer (but in reality not so simple answer) is the presence of other animals that serve as a vector for M. bovis. In New Zealand, the principal reservoir is the brushtail possum (Trichosurus vulpecula), in Michigan (USA) it’s white tailed deer (Odocoileus virginianus) and in the UK the Eurasian badger (Meles meles). In each country the test and slaughter method has managed to almost entirely wipe out M. bovis from cattle, drastically reducing rates particularly in the 1950s and 1960s, until around the 1980s where M. bovis makes a massive comeback. In the UK particularly, rates of bovine tuberculosis in cattle have increased rapidly and equally as quickly spread to other farms.

As a result of these vectors, which provide a large reservoir for M. bovis, it makes the typical control methods insufficient to completely eliminate the disease. This means that the continued re-infection of herds previously cleared of bovine tuberculosis becomes a considerable problem, as like its human cousin M. tuberculosis, M. bovis takes its time in causing any visible disease. This means an infected animal can fly under the radar for months exhibiting no particularly visible signs of infection and be excreting dangerous numbers of infectious bacteria in its sputum, feces and other excretions. As a result where M. bovis infection is rampant, there is a considerable economic burden on farmers in terms of more regular tuberculin testing, herd movements being locked down (put on restriction) until they pass two clear tuberculin tests and the overall loss of animals.

As many of you are probably thinking, the best way theoretically to control a vector borne disease is surely to directly control the vector and vectors that prevent the elimination of M. bovis. A particularly attractive option on the surface is to engage in a mass elimination of the potential vector from around farmland, to attempt to prevent contact between the infected vector and uninfected cattle. Unfortunately the way things work in reality is often much more difficult than theory. Compared to the large numbers and difficult terrain that the possums have on their side in New Zealand, in the UK badgers are implicated as the vector and are not particularly difficult to find as they leave obvious marks of their habitation. A large scale cull should be the obvious solution except for one key problem: The British love their badgers.

There is a considerable conservation and animal rights movement in Britain that heavily opposes any potential cull of badgers. As a result the control of M. bovis has become a considerable political football with two sides, farmers who want to cull badgers and animal rights organizations that claim badgers are being used as a ‘scapegoat’. With neither side giving an inch and the decision about the next potential badger cull to come soon; the UK debate about the best means to control M. bovis raises an important question as to how scientists, government officials and the public should interact in the control of infectious diseases.

In solving this, numerous lines of inquiry will have to be explored to determine what the best solution that all sides could agree on would be. Firstly, it is worth looking at the biology and history of Mycobacterium bovis that make it such a successful pathogen. Then in terms of resolving this debate, it’s essential to determine the role that the Eurasian badger plays in the spread and persistence of M. bovis in the UK against other potential factors.

Once the link between M. bovis and the badger as a vector has been established, an analysis to see what benefit (if any) that culling would present on reducing herd breakdowns (confirmed cases of bovine tuberculosis in a cattle herd). Finally an analysis of other potential solutions other than culling such as ‘wildlife friendly farming’ and particularly vaccinating badgers. Finally, after these factors have been considered, we’ll revisit the original question and discuss what sort of compromise between health officials, farmers and conservationists could work.

Join back tomorrow for part II of this series: What makes Mycobacterium bovis such a problem?

Recommended reading

Although I haven’t cited anything in particular for this introduction, there are a lot of papers on this topic and there are a few that are particularly useful in understanding what will be discussed over this week here. If you have access to pubmed or other search engines, a read of some of the following papers would be recommended although not strictly required as they will be discussed in detail as the series goes on:

Donnelly C.A., R. Woodroffe, D.R. Cox, J. Bourne, G. Gettinby, A.M. Le Fevre, J.P. McInerney and W.I. Morrison (2003). Impact of localized badger culling on tuberculosis incidence in British cattle. Nature, 426:834-837.

Donnelly C.A., R. Woodroffe, D.R. Cox, F.J. Bourne, C.L. Cheeseman, R.S. Clifton-Hadley, G. Wei, G. Gettinby, P. Gilks, H. Jenkins, W.T. Johnston, A.M. Le Fevre, J.P. McInerney and W.I. Morrison (2006). Positive and negative effects of widespread badger culling on tuberculosis in cattle. Nature, 439:843-846.

Griffin J.M., D.H. Williams, G.E. Kelly, T.A. Clegg, I. O’Boyle, J.D. Collins and S.J. More (2005). The impact of badger removal on the control of tuberculosis in cattle herds in Ireland. Preventative Veterinary Medicine, 67:237-266.

Gilbert M., A. Mitchell, D. Bourn, J. Mawdsley, R. Clifton-Hadley and W. Wint (2005). Cattle movements and bovine tuberculosis in Great Britain. Nature, 435:491-496.

Krebs J.R., R.M. Anderson, T. Clutton-Brock, C.A. Donnelly, S. Frost, W.I. Morrison, R. Woodroffe and D. Young (1998). Badgers and bovine TB: Conflicts between conservation and health. Science, 279:817-818.

Phillips C.J.C., C.R.W. Foster, P.A. Morris and R. Teverson (2003).The transmission of Mycobacterium bovis infection to cattle. Research in Veterinary Science, 74:1-15.

Carnival of the wee animacules

Although I'm a little late on this one, the carnival of the wee animacules has been posted at Science and Politics.

Thursday, March 23, 2006

Canwest apologises

Canwest who own the TV station C4, which boldly decided to show the South Park episode "Bloody Mary" that offended just about every Catholic in New Zealand, has decided to apologise.

Broadcaster C4 says it is very sorry for any offence it caused by showing the controversial South Park Bloody Mary episode.

In a statement the broadcaster says the Standards Committee did not uphold any of the formal complaints it received about the show, which showed a statue of the Virgin Mary menstruating.

But C4 chief operating officer, Rick Freisen, sincerely apologised for any offence taken and said the broadcaster would not repeat the episode even though it is allowed to do so.

I'm so very convinced that they are being very sincere and that it isn't due to other factors like potential boycotts or similar. In any event I must pass my congradulations to C4, seeing as they've happily decided to donate whatever spine they may have had and I can assure you, spines are something that is hard to come by in the media these days. Maybe someone else can find a use for it.

[Note: No offence to our invertebrate masters is intended by this post]

Tuesday, March 21, 2006

Bloody trackback spam...

I've had to delete over 30 assorted trackbacks from various sites spamming online poker to irritable bowels anonymous or something. I'll take it as a sign that I must be getting popular.

Monday, March 20, 2006

Bioessays journal editorial and reflections

Thanks to PZ Myers, I was introduced to a journal I had not encountered before called Bioessays that I've become a dedicated reader of ever since. They often publish some interesting evolutionary hypotheses, particularly on subjects of my interest such as the immune system and origins of vertebrates. Recently, the editor Adam S. Wilkins has decided to write a piece about Intelligent Design and how scientists should approach the subject. I particularly like his concluding paragraphs, which I'll quote here as the paper probably isn't free and I think he's made a very pertinent point:

Furthermore, those scientists with passionate anti-religious convictions should accept that Science can no more disprove the existence of a Deity or immortal souls than religious people can prove the existence of either. More tolerance of private religious belief, coupled with insistence on what scientific evidence does actually tell us about the history of the world and living things, would be appropriate.

If, in contrast, scientists insist on atheism as the only ‘‘logical’’ belief system or demand that people choose between ‘‘evolutionism’’—the quasi-philosophic belief in evolution as a guide to what should be—and belief in God, the outcome is not in doubt. More than half the people in the
U.S. would choose religion and reject the science. The consequences of this would be far wider than simply the confusion of school children about the history of life on this planet. Once one has rejected scientific evidence for an ancient Earth and a long evolutionary history of living things, it becomes correspondingly easy to start denying other scientific evidence, for instance evidence on climate change, resource depletion, the nature of pandemics, the causes of species extinction and much more.

I fully agree with this with the caveats that we shouldn't be afraid to admit that many prominent atheists do think that evolution strengthens their position. For example, Richard Dawkins (who always seems to come up) has stated that "Darwin made it possible to be an intellectually fulfilled atheist" and Paul Myers from Pharyngula has written several pieces on how he feels, which I recommend reading incidentally. This is usually used as some sort of launching point that all evolutionists are atheists and that evolution degrades religious beliefs blah blah blah froth at the mouth blah blah whatever. I think some introspection here might be of some use.

Here's a little story for those who are interested in reading a bit of (probably somewhat incoherent in places) rambling about my reasons for my faith. About 6-7 years ago after probably one of the worst years of my entire life, I lost my faith in God and rejected Christianity completely. I really was a very bitter and angry fellow at the time, having felt that God had deliberately tried to do me in, my family, my friends and virtually everyone else I knew. Because of these rather bad experiences and my already considerable dislike of religion that had been building for a while, I became what most would identify as a "strong atheist". My atheism at the time was directly the result of what I saw around me, such as problems with family members and friends, the world in general and my general angst as an angry young man (And I mean angry).

Science never really came into the picture for my rejection of Christianity and God at the time. You could attribute that to more to general angst and general disillusionment with religion. In fact, I probably wouldn't have cared less about what science had to say on the nature of God because having gone to a Catholic school, nobody ever introduced me to the concept that religious concepts would be directly contrary to science anyway. This of course never became overly relevant, because even with my initial introductions to creationism of the full YEC variety on university bulletin boards and with someone handing me Behes Black Box in my first year of university. Although I only had a relatively poor grasp of science at the time, there was something that never quite made sense with the arguments of the YEC creationists/stealth creationists that I debated with.

I have to concede that creationism merely reinforced my atheism at the time. In fact, I thought Christianity was more ridiculous after encountering creationism than I ever had before. Yet, although this might sound somewhat odd after what I have written just now, I did inevitably regain my faith in God and am unashamed to admit that I'm Christian. Bearing in mind that I was formerly Christian, then became an atheist and now went back, this would seem to make me a 'flip-flopper' I guess one could say. The main thing that made me rethink about things was the Christians I met at University during my second year (and beyond).

I've always been one for actions rather than anything else and I was very impressed with the Christians I met. I found they weren't the general hate mongers that I had frequently come to associate with Christianity like Fred Phelps and Pat Robertson. Many of them are among my best friends still and people who I probably get along best with. I also lost my impression of general Christian bloody minded fundamentalism from my association with these people. I found that many Christians hold a wide range of views on various topics, including scientific ones like evolution, social issues and about the bible itself. Most importantly, I liked the attitudes of many Christians I met, the way they treated others and the fact they still retained a genuinely held belief in God that I once had.

After a lot of reconsideration, I came back to God after careful introspection and decided that many of the core beliefs of Christianity still made sense to me. I should point out that I've never regarded the bible as literal and in particular I've always regarded many stories in the bible as being allegorical or poetic in nature to demonstrate a point, but not be literal history (where they simply fail to make sense, despite what creationists may protest about). In many regards however, I never allow my faith in God, based entirely on reasons from my own introspection to hinder how I view or observe the world around myself. I keep my science as science and God as faith, which I soon found after asking various Christians I met was not an uncommon view.

And so in the end I came back to God and I can even say that I have a more strongly held faith than I did before I lost it originally. This is probably because of the fact I've had a longer time to think about things, but also because my knowledge and general opinions have matured a lot more than what they were. Plus, I'm not as angry anymore, well except when debating where I still can dish out a bit of sass.

I suppose after such a lengthy rant, which was entirely unplanned so it has no real particular point, I should get to whatever it is I'm trying to say. Quite frankly, I don't care if Dawkins (or any atheist) says that evolution allows them to be certain about their atheism. It doesn't particularly bother me, because science isn't something I regard as being in conflict with my belief in God. If I held my belief in God as something that is in conflict with science, maybe I would regard the statements from the likes of Dawkins as threatening and proof of evolution destroying Christianity or some similar nonsense. We shouldn't hide the fact that knowing what is good science is something that a lot of groups, such as atheists, will claim as something that supports their view. Personally, I think evolution and the way nature works is a testament to the power and creative ability of God. Like Adam points out in his editorial that I agree with so much, I can't prove to Dawkins what I believe and Dawkins would have a [probably] impossible time using science to convince me God doesn't exist.

Of course, atheists are almost the 'boogeyman' for Christianity and have been promoted to that spot far too prematurely. I find that it's Christians that are degrading Christianity more than anything else. Those who want to hold concepts like creationism/ID being opposed to decent actual science are doing more harm than they are good, but probably only minimal damage in the end. It's individuals who proclaim that Christians should follow their general bilge and rhetoric like Pat Robertson, Fred Phelps, Kent Hovind and Anne Coulter that do more damage to Christianity than any science ever could. If you ask atheists or those who reject Christians beliefs about the sorts of 'Christians' they have in their minds, they'll tell you about the loud mouthed dribbling of the likes of the above as what their impression of general Christianity is.

The response of numerous Christians demonstrates that not even 'we' like them overly much. There are not many Christians who would like to concede that Fred Phelps, who protests at the funerals of soldiers with his band of escaped lobotomy patients, is a Christian himself. We just shove aside the fact he publicly claims he is Christian, because we know that he isn't following the tenants of Christ in spitting out his virulent spiels about homosexuals or whatever. Unfortunately, he's loud, he's very much in the media spotlight with his antics and these actions speak almost as loudly as the failure of the general majority of Christians to oppose and publicly criticize their ridiculous assertations.

If you ask me what is driving people from churches, making people question their faith and generally degrading the position of Christianity as being relevant in today’s world, it's the lack of moderate Christian voices against fundamentalism.

Blogging this week

I'm a little behind on my reading due to watching the Black Caps give the West Indies what-for in the test matches, so most of the stuff I wanted to write about will be a little delayed. I'm currently looking into the plans to cull badgers in England, which will be the subject of discussion this week and I'm still planning on writing more about the evolution of the immune system (TLRs part II). Other stuff to follow will be more about one of my favourite topics (antibiotic resistance) and I'm looking into alternative theories about what caused the black death as a follow up to this post.

In any event, well done to the Black Caps for a well deserved test series win and without the distractions of the cricket there should be more blogging (hopefully).

Friday, March 17, 2006

Excellent new blog

Good Math, Bad Math by Mark Chu-Carroll is a new interesting blog that covers pseudosciences love of abusing mathematics. I first noticed this blog when Mark did a take-down of the horrific statistical analysis used in the latest paper produced by the Griers at Respectful Insolence. He's since moved onto different subjects now including analysing the mathematics of William Dembski. I highly recommend a read.

Skeptics cirlce posted

The 30th Skeptics Circle is now up and ready for skeptical minds at Paige's Page. This one is quite big with quite a few particularly interesting articles, with possibly a submission from Kelly Jolkowski being one of the best. Essentially, her son Jason has been missing and in her families desperation they turned to 'psychic' help. Unfortunately, she has found that the psychics aren't quite able to live up to their claims and she has a blog dedicated to discussing the numerous frauds and psychic conartists she has encountered. There are numerous other great articles too as always, so head on over and get to some reading!

Thursday, March 16, 2006

Amazing quote

There are few quotes that are said today that come off as being both very pertinent and insightful, but this one from Jamie Raskin a professor of law from AU is right up there. Speaking in opposition to a bill that would propose a blanket ban on homosexual marriage, the republican senator presumably thought they were being witty when they began the following exchange:

At the end of his testimony, Republican Senator Nancy Jacobs said: "Mr. Raskin, my Bible says marriage is only between a man and a woman. What do you have to say about that?"

Raskin replied: "Senator, when you took your oath of office, you placed your hand on the Bible and swore to uphold the Constitution. You did not place your hand on the Constitution and swear to uphold the Bible."

The room erupted into applause.

I don’t think that poor Jacobs would have had any response to that.

Wednesday, March 15, 2006

Gay genes and sperm donors

Scientists really should avoid putting their foot in things sometimes:
A Christchurch scientist [Dr. Frank Sin] has drawn the ire of the gay community and fellow scientists by saying infertile couples should be told if their potential sperm donor is gay because of evidence that homosexuality is genetic
I think this is frankly ridiculous. Yes, homosexuality probably does have some degree of genetic basis that is probably further conditioned by the environment an individual grows up in. The problem here, that I can see, is that it puts a gay donor into some sort of category like they have a disease. Further, this is only one step away from starting to specify what sort of characteristics children should have. Perhaps we should start having parents who are dark haired give 'informed consent', because maybe I don't want a kid with dark hair. Maybe we should extend it to donors who are of specific ethnicities as well, perhaps using the justification of higher rates of diabetes, certain cancers or heart disease as the reason.

This is just ridiculous and I certainly hope nobody takes this recommendation seriously.

Tuesday, March 14, 2006

New Zealand HIV rates rise 17%

This report I saw over at scoop magazine is somewhat concerning, indicating that there has been a fairly substantial increase in the rates of HIV transmission across the board.

Of the 183 new diagnoses, 89 were men-who-have-sex-with-men (up 19% on 2004), 73 (35 men and 38 women) were infected heterosexually (no increase on 2004) and six were children diagnosed with HIV through mother-to-child transmission, four of whom were born in New Zealand to mothers who had not beed diagnosed with HIV. There are now more people living with HIV in New Zealand than ever before.

“What this tells us,” said New Zealand AIDS Foundation Board Chairman Hoani Jeremy Lambert, “is that no-one in New Zealand can afford to be complacent about HIV. Treatments might have improved but this is still a deadly serious virus. It has a major impact on health and wellbeing and people still die prematurely, especially infected children.”

I have this disturbing feeling that so much of this could be related to the presence of anti-retrovirals making individuals too complacent. In the minds of many, these drugs have 'cured' HIV so it's no longer as dangerous to go and have unsafe sex. This is far from the truth however as the article mentions:
“The medicines delay the progression from HIV to AIDS but they are not a cure and they do not prevent transmission of the virus to others,” she said. “Prevention is still our best option. A properly used condom is close to 100% effective against the virus and HIV screening of all pregnant women would practically eliminate mother-to-child transmission.”
I think the ABC strategy that worked so well in the past is worth repeating. It's essentially Abstinence, Be faithful (Monogamy ftw) and finally Condom use. Another good idea I think would be to make sure that highschoolers are given better sexual education, which would hopefully leave them better informed about how STDs behave and spread.

Insanity of War.

World War 2 has been an interest of mine since I was still in high school and over time I’ve read pretty much anything about it I could get my hands on. Of all the authors and various books written about WW2 two of the best are arguably Stalingrad and Berlin, which were both written by Antony Beevor. These two books changed my opinion on World War 2 more than anything else because both accurately and clearly detailed the depth of insanity men fall towards in war.

One of the most poignant examples of this was when a group of German soldiers (If I recall correctly, they may have be Russian) were burying one of their comrades. They covered the man with branches collected from nearby trees, when one of the other soldiers cried out that they were “Enemy branches!!” causing the soldiers to fanatically recollect the foliage and burn it. Another example was a German solider facing the huge soviet offenses to charge to Berlin in 1945, comparing the attacking Russian waves to animals that were simply out to be killed or kill him. The Russians of course weren’t terribly better with many Russian soldiers, still incredibly bitter from the siege at Stalingrad, going on a murdering and raping spree against German civilians in order to get revenge.

The violence, inhumanity and sheer disregard for human life demonstrated on the Eastern front of WW2 demonstrates war at its very worst. Russian commanders in their attempts to race to Berlin to beat the Americans, not to mention each other, wasted huge amounts of human life. This is because the Russians frequently chose to attack using large bludgeoning waves of troops against well entrenched positions. Casualties, even considering the small numbers of German defenders, were often extremely high and better firing support, reconnaissance and preparation before attacks Russian commanders could have avoided such high losses.

Adolf Hitler also played his part in exacerbating both the war and the loss of human life. Hitler held to an untenable position where he would not concede even an inch of land that his forces had previously gained. This resulted in long, bloody and most importantly pointless sieges such as Budapest, which I get the impression Hitler thought he could turn into a German equivalent of Stalingrad. Hitler too was also completely deluded, at one point ordering phantom divisions that never existed and engaging in wasteful assaults such as the Ardennes campaign of 1944. Panzer divisions lost in that attack would have been better served on the eastern front, which would have been more useful than simply being easy targets for American and British planes.

Unfortunately, the western Allies are not entirely guilt free from (needlessly) adding to the already horrific death toll of WW2. The fire-bombing of a small German city called Dresden in February 1945 demonstrates a similar mindset in many ways to the revenge rapes/murders on civilians carried out by the Russians. Dresden had no important industry, was not in any area that would be essential for allies to cross and had a small population. The town was almost entirely annihilated by the combined American/British air raid and over 300,000 people were killed. The air-raid was nothing more than a revenge attack for the bombings on British cities (1941) and the V-2 rocket attacks (~1944-1945).

Although I’ll concede that world war 2 was a war that needed to be fought as the evils of NAZI German and Imperial Japan needed to be combated, what never needed to happen were so many incidents where peoples lives (regardless of what side they were on) were destroyed for no purpose. Such are the depths that wars frequently sink towards, where human lives become nothing more than little plastic figurines on a table to be cashed in for more territory, materials and prestige.

Sources: Berlin: The Downfall 1945, and Stalingrad both written by Antony Beevor and more than worth reading even if WW2 isn't your area of interest.

Monday, March 13, 2006

Awesome menu!

This is the best restaraunt menu I have ever seen before. From the "Carbon burns fresh particularly must" to the "Carbon burns fatty cow New Zealand", which I will leave to you to figure out what they are implying there, this is probably one of the most interesting menus I have ever seen. There is more hillarity as well and I'm still trying to figure out if this is just an elaborate hoax or not.

(Spotted at Pharyngula who spotted it originally at Helminthlog. If I was psychic I would predict this going around the blogosphere fairly quickly)

Amazing game of cricket

It's not every day when you see a game of cricket have over 400 runs hit in one innings, but when it does happen it's an incredibly amazing event. Of course, I have to concede that when it's Australia vs. pretty much anyone and you see Australia get 434, you don't really expect the other team to beat that. This naturally led to several Australian fans posting messages such as this one on the tonk blog (a part of the Sydney Morning Herald).

"Could there possibly be a hole deep enough for Smith by the end of that innings- We'll see now who chokes under the pressure of having to get 435 to win.

I predict the record for the greatest winning margin will also go tonight."

Unfortunately for this particular Australian cricket fan (Quin), he's going to look mighty silly because South Africa pulled off an absolute blinder to win the game. I could watch cricket like that any day, especially when Australia lose ;) I can tell you what though, I would not want to be a Mr. Lewis on his way back to Australia any time soon. The Australian media, which is in shell shock at the moment, is going to recover they are going to eat Lewis alive and Ricky Ponting (the Australian captain) is going to be dessert.

Sunday, March 12, 2006

Now this is televangelism

Jay from Ocellated posted a link to this devious little idea to spice up a televangelists show. Robert Tildon while getting into his televangelism, stops inexplicably every so often, grimacing and screwing up his face in odd ways, apparently claiming the "Holy Spirit" is writing around in him (I'll put my money on hot mexican beans!). In any event, such pauses only call for one thing: the addition of the wonderful sound of flatulence! Farting Preacher accomplishes this goal, with several edited videos that add these most delightful of bodily noises on cue to his show.

Now that's my kind of televangelism. As smelly as it is a dirty and underhanded way of taking advantage of peoples beliefs.

Awesome rant

This is very easily one of the best rants I've ever read:
I'm not satisfied with quick non-answers to hard questions. I possess both righteous indignation and humility in the face of ignorance. I reject the idea that religiosity automatically makes someone an expert on anything, especially matters of science. And I just might know what the hell I'm talking about. Who the hell do I think I am, spouting such arrogant, highbrow bullshit?
Well said indeed by Evil Monkey (of closet fame) and the rest of the rant pretty much hits the nail on the head on a wide variety of issues, including how science is popularised in the media, ID and the life of most young prospective scientists.

Saturday, March 11, 2006

Zardoz!

While reading pharyngula earlier, I encountered a link to a review of a movie called Zardoz. I have to admit, that review convinced me that movie is comedy gold in the making and I'm not going to have to see it. There truly is such a thing as a movie so bad, it's actually good! Besides it has Sean Connery in it, he couldn't possibly do anything wrong right?

Friday, March 10, 2006

Revisting probiotics

Although the last time I wrote on the subject of probiotics was somewhat pessimistic in tone, it should be emphasized that I think the entire concept is a really good idea. For one thing, bacteria as a general rule have a bad reputation among the general public that is worse than any other group of organisms. After all, microbes are linked to terrorism, disease, cooties and generally thought of as being associated with unhygienic practices. The number of people who cringe at the idea that milk is consistent mostly of bacteria is quite substantial. Very clearly, microbes have a major public relations problem and probiotics are a way of conveying to the public that there are ‘good guys’.

In fact, before I continue with the remaining substance of this post, I should point out the majority of normal bacteria aren’t out to get you. Microbes do numerous important things for every person on the planet and all completely without thanks or even a simple acknowledgement. For example, one of the most important functions bacteria that live on your body is to inhibit the growth of pathogenic microorganisms that try to establish themselves. As a further bonus, the gut microflora may communicate with the immune system, helping to appropriately target hostile microorganisms (see references of the previous post and below for some more information).

Obviously, these facts are essentially the basis for probiotics and what makes them such attractive options for treating certain illnesses. How exactly probiotics are supposed to do so and if they are even effective is somewhat under contention. To discuss this, some questions that arose from a comment left by impatientpatient are worth addressing below.

To begin:

1.VSL-3 is a fairly new product on the market and has specifically been tested on colitis, I believe, at the University of Alberta. It was a tiny study with what looks to be promising results. Pain and dysfunction was relieved a a fair majority of patients using this. Is this a place to start in seeing if probiotics or blends work?
Almost certainly, although small study sizes can only give indications that something is working or not. A much larger study that follows people for a longer period of time is required to definitively establish a protective effect, but many initial results do look good. The science is there to suggest probiotics can be an effective treatment for certain inflammatory bowel disorders, which are predominantly thought to be caused by abberant immune reactions between the native microbiota and the host immune system.

2.I was fortunate to have a doctor that recognized C Diff when she saw it. But I continue to have flare-ups of excuciatingly painful magnitude (drop to the floor clutching my stomach) on occasion a year after this infection.


I did use Lactobacillus Acidophilus, as Flagyl and Vancomycin pretty much have a fair bit of a failure rate. It was an education, trying to find something that would benefit me in any way. Yeast- used like pool shock once, and lactobacillus and time seemed to resolve the acute infection. I do not know why I continue on occasion to be in pain and all, but a dose of lactobacillus seems to help.

Herein lies the problem. As a patient, I decry pseudoscience. I would like to know if somthing has efficacy and why- I am not about to take anyone's word for something these days without researching it extensively. I think that is not a terrible attitude to have. I did research probiotics and I did find what seemed to me a plausible cause and effect- over the short term only. But until someone does a giant study-- and a proper double blind placebo trial- I rely on a fairly sketchy body of evidence. Was it LB, time or placebo effect that caused my condition to lessen? I don't know. I hope it wasn't the placebo effect. I hope it was a combination of time and LB.

Without any direct familiarity with the particular disorder and what may be going on, I would possibly guess that the Lactobacillus acidophilus may be helping. At the same time, it’s possible that the probiotic isn’t doing anything other than aiding the reestablishment of the microflora. The original infection of the Clostridium difficile may have thrown things out of whack and the antibiotics compounded the problem. All that may have been required was some time to reestablish the microflora and put things back to semi-normal. I could imagine that flare ups may reoccur after a subsequent encounter with another pathogen (not always another bacterium at that), with the resulting immune response re-activating ‘confused’ immune cells that attack the normal microflora again.

3. The other problem is that many doctors have really no idea of how horrid C Diff can be. And many do not recognize it. That can cause C DIff to morph into colitis, Crohns and even death. How can this be addressed?
There really isn’t a lot that can be done here except to educate and retrain doctors. In many respects the worst aspects of disease is that the early symptoms are all very similar. For example, most cases of meningitis start as something that just looks identical to the flu and can be very easily misdiagnosed. As New Zealand is currently experiencing an epidemic of bacterial meningitis, caused by Neisseria meningitidis, this issue is a considerable problem. With many diseases the line between a painful long lasting disorder or even death, can often be the time between onset of symptoms and recognition and treatment of the disease at early stages. The response from health authorities here was to provide more information to the general public to spot symptoms, promote greater awareness of the disease among health authorities and analyse potential cases more closely.
4.How can you measure gut flora in people? And could you do an experiment that did this before, during and after treatment with probiotics? NEOPHYTE but curious. Can stool cultures be helpful in this regard? Could you measure levels of C Diff and probiotics in a stool culture?

There are several ways of analyzing the gut flora of people and the majority of methods all involve pooh in some way. The first method is to simply take a nice slice of waste material, set it up on a microscope slide and eyeball what is there. Generally, you can find a lot more microorganisms by such cursory examinations than you can manage to actually culture. Obviously, looking at a bunch of rods, cocci and various squiggly things isn’t actually going to tell you overly much.

As a result, molecular methods are a much better way of finding out what the microbiota actually consists of. The way this is done is by exploiting wide amounts of natural variation among different bacterial strains in their 16S ribosomal RNA (rRNA) sequences. This little gene is useful because it has some regions that are constant (not changing) and other parts that are hyper-variable and change a whole lot. This allows scientists to easily amplify a range of 16S rRNA fragments by a technique called PCR (Polymerase chain reaction). These sequences can be separated out by gel electrophoresis and sequenced to identify what organisms are present. During an experiment, an investigator can determine if known bacteria are present before, during and after an experiment, so the answer to the second part of your question is also yes.

Of course this “poo print” has its problems, which a paper in Science by Eckburg P. et al illuminated quite clearly. The first problem is fairly simple, what bacterial species we have identified conclusively through sequencing is a tiny part of what is really there. We may be able to identify general groups of bacteria, but for families we don’t really have a lot of information on it makes identification hard. The other problem comes from the fact stool cultures are used as a model for the entire gut microbiota. This may not actually reflect reality very well, as some species may not be present in high numbers or may be hard to detect for other reasons.

Lastly of course, because this is a molecular technique that can work off even a single strand of 16S rRNA (theoretically at least), it’s difficult to verify the exact numbers that an organism is actually present in. This is one of the other problems with probiotics as a whole, you may be able to show they are present and possibly even persist, but the probiotic organism may end up an oppressed minority and not be able to affect anything.

On the whole however, I see a considerable amount of benefit to the use of probiotics, especially to recover from using antibiotics and serious infections of the gastrointestinal tract like Clostridium difficile. Obviously, more basic work needs to be done on the gastrointestinal tract microflora, particularly on how they interact with the immune system and which members are prominent in this interaction. This research would have obvious benefits to the understanding of probiotics as well.

References

Eckburg P.B., E.M. Bik, C.N. Bernstein, E. Purdom, L. Dethlefsen, M. Sargent, S.R. Gill, K.E. Nelson and D.A. Relman (2005). Diversity of the Human Intestinal Microbial Flora. Science, 308:1635-1638.

Patel J.B. (2001). 16S rRNA Gene Sequencing for Bacterial Pathogen Identification in the Clinical Laboratory. Molecular Diagnosis, 6:313-323.

Carnival of the wee animacules is up

The third meeting of the wee animacules carnival is now up over at Aetiology. It's a special one at that, because it commemorates a once a year special occasion, the birthday of the much loved Paul Myers from Pharyngula. Presumably punch and birthday cake can be found at his blog.

Snuppy the puppy is..... *drumroll*

A clone! As it turns out, although Hwang managed to basically humiliate the entire field of stem cell research by fraudulently falsifying data, at least the dog Snuppy is 100% genuine clone. Two studies published this week in Nature, by two independent groups one led by the Seoul National University Investigation Committee and the other by Heidi G. Parker et al show conclusively Snuppy is a clone. Interestingly though, the paper by Heidi G. Parker et al indicates the group is still somewhat skeptical of the overall result, citing several problems with a totally conclusive assessment of their results.

Firstly, they note they did not personally draw the blood samples used by them in the experiment but a third party did. They don't anticipate this to be a problem however, but probably mentioned it for completeness in case the result was disputed (which looks unlikely). Additionally, they were not provided samples from the original oocyte (egg) donor, which was tested by the SNUIC, so they cannot make a definite assessment of if the results from the mitochrondrial analysis they attained were expected.

Overall however, I think we can now bury the hatchet over the whole question if Snuppy is a clone or not.

Thursday, March 09, 2006

Farm animal cannibalism strikes again?

Cannibalism is one of those practices that, at least as far as humans go isn't very high on the list of things that are socially acceptable. One of the numerous problems with cannibalistic practices is the transmission of diseases, after all what infects dinner is just as easily going to infect the cannibal. It should be reasonable common sense as a result not to feed a farmed animal the remains of their fellow animals. This would greatly aid the spread of an infectious microorganism through a herd and possibly even rapidly increase virulence (which is often directly correlated to the ease of transmission).

The case example of why this practice shouldn't be performed, with any animal, is the dramatic outbreak of bovine spongiform encephalopathy (BSE) in Britain. BSE was found to be spread by an infectious protein called a prion, which is predominantly found in the brain and spinal matter of the remains of cattle. Worse, these parts were frequently fed back to other cattle as a supplement to their feed, providing an easy method of transmission for the infectious prions. The worst part of the entire discovery was not just that other cattle could be infected in this manner, but the potential spread of the disease between beef from infected cattle and humans. This led to the culling and suffering of a large number of animals and an overall ban on British beef that lasted a considerable time.

The entire result was a heavy economic and consumer confidence toll on British farmers and on the entire beef industry that cost millions (billions?) of pounds. Predictably, the practice of feeding dead cattle back to other cattle was immediately halted. With such a brilliant example of why allowing cannibalism with farm animals is a silly, you would probably imagine that most places would ban the practice regardless of species. Unfortunately, an outbreak of a disease among pigs on South Island farms recently in New Zealand, may be linked to feeding pigs the remains of other pigs imported from overseas (emphasis in the quote below is mine and I shortened the length, indicated by the ….)

An animal health expert says a pig disease that has struck the heart of New Zealand's pork industry is almost certainly Post-weaning Multi-systemic Wasting Syndrome (PMWS).

PMWS is a highly contagious viral disease that kills young pigs up to 12 weeks old. It has forced the closure of about six pig farms in the North Island.

Vets have been investigating a disease outbreak that has so far killed about 1,000 piglets on eight to 10 farms near Christchurch in Canterbury.

……………

He says it is possible that the Canterbury PMWS outbreak has been caused by infected imported pig meat being fed to pigs in foods scraps.

Feeding waste material to pigs has recently been banned again.

Obviously this is a severe disease and has resulted in a heavy economic loss for several farmers. The disappointing part is that lessons of the past from the emergence of BSE clearly weren’t heeded, especially if the outbreak is conclusively found to be linked to cannibalistic practices. Although the disease, called Post-weaning Multi-systemic Wasting Syndrome or PMWS is not suspected to be dangerous to humans, the outbreak still demonstrates important principals about how diseases may result from farming practices.

PMWS is caused by a virus called porcine circovirus 2 (PCV2), which was first identified in 1997 and is probably one of the most puzzling diseases around. PMWS is diagnosed not by using molecular techniques such as antibodies, but instead through the manifestation of certain symptoms that occur over the course of an infection. This is because antibodies to PCV2 can be detected amongst herds that do not show any overt signs of disease, indicating the organism is present but inexplicably not causing an infection. As a result, the following clinical symptoms are used to describe the disease: wasting (rapid loss of body weight), dyspnea, enlarged lymph nodes, diarrhea, pallor (loss of skin colour) and jaundice. Additionally, in some cases animals may exhibit coughing, pyrexia (a fancy term for fever), gastric ulceration (often leading to anemia), meningitis (an infection of the meninges surrounding the brain) and dropping dead (which is terminal).

How PCV2 causes such a wide array of symptoms and even how it initiates disease is the puzzling aspect about it. Experimental animal models have largely failed to reproduce the disease by using PCV2 by itself except in certain cases. Interestingly, more success has been attained when PCV2 was injected with other viruses, such as Porcine parvovirus. Regardless of the mechanisms that determine if the virus becomes infectious, when PCV2 does it targets some of the most vulnerable members of the herd, namely piglets aged between 7-15 weeks old. Possibly the most striking characteristic of PMWS is the overall mortality rates in infected animals, potentially getting as high as 40% and can even induce pregnant sows to abort their fetuses.

Dealing with the virus is equally difficult, because it tends to be widespread throughout the herd and circoviruses are notoriously difficult to kill with antiseptics and detergents. Containment and control requires more practical, such as reducing herd sizes, keeping animals separated by age and reducing animal density. As can be seen, the biology PVC2 and the linking of the outbreak to imported pig meat being used on the farms, raises an intriguing hypothesis as to the potential aetiology of the disease. Let us imagine a potential scenario from a land far, far away….

On a farm in an unknown land, a sick piggie called Mr. Pork wakes up to a pretty bad headache among other things…

Mr. Pork: Owww my head, I feel under the weather here. I know, I’ll go to farmer Brown for help! He’ll know what to do!

Farmer Brown: Why hi there porkie, how’s your day going?

Mr. Pork: I’m feeling a bit under the weather here and I may be getting ill!

Farmer Brown thinks to himself: I’d better do something about this before it spreads!

Farmer Brown: Well I have just the solution there Mr. Pork, we should go and visit Dr. Mallet. He’ll fix you all up!

Mr. Pork: Oh that sounds great, let’s go and –

Image hosting by Photobucket. Image originally from an article written by the onion www.theonion.com*CLUNK*

Farmer Brown: Off to the sausage factory for you!

Later at the pork to sausage factory….

Worker 1: What are we going to do with all the left-over pig bits?

Worker 2: Let’s package them up as supplemental feed and send them to New Zealand.

Worker 3: Genius!

Anyway, returning from the realm of imagination, there may be solid indications that this is a possible origin of the PMWS outbreak in New Zealand. The suspected causative agent PCV2 has already been widely identified in New Zealand pig herds, and has caused outbreaks in the North Island previously. It is theoretically possible that a disease transmitted from infected pigs overseas, such as a different serotype of Porcine parvovirus that is not immunologically present here in New Zealand was in the imported meat. Once fed to the pigs on the farms in question, it encountered the ‘native’ PCV2 and potentially triggered the silently waiting virus to a full blown infectious disease.

Of course, this is not the only explanation but given the biology of the disease it’s a fairly compelling place to at least make a start. This is of course where one would expect the government to step, but unfortunately, it doesn’t actually appear such assistance is going to be quite what some farmers may expect:

Canterbury pig farmers at the centre of a disease alert have been given a clear message from the government that it will not step in with an eradication plan.

The Ministry of Agriculture and Forestry's Biosecurity Authority has advised the government that eradication of the suspected disease, PMWS or Post-weaning Multi-systemic Wasting Syndrome, is not viable.

Well, that almost sounds to me as if they are throwing in the towel before they even try to do anything. At the very least, by identifying why the outbreak occurred and potentially trying to contain or eliminate the cause authorities could do a fair amount of good. While I do suspect that elimination of PVC2 may be unfeasible although containment and other measures should at least be attempted. If there is a positive to be taken from the recent outbreaks, it’s that feeding pig remains back to other pigs has been re-banned. I guess you take your victories where you can get them.

References

Chae C. (2005). A review of porcine circovirus 2-associated syndromes and diseases. The Veterinary Journal, 169:326-336.

Darwich L., J. Segal and E. Mateu (2004). Pathogenesis of postweaning multisystemic wasting syndrome caused by Porcine circovirus 2: an immune riddle. Archives of Virology, 149:857-874.

Harding J.C.S. (2004). The clinical expression and emergence of porcine circovirus 2. Veterinary microbiology, 98:131-135.