A nice statement ...

No matter where one stands on the spectrum of perception and worldviews…the “state of being” these words reflect serve as a sound guide...they fly sound and true.

I believe in time,
matter, and energy,
which make up the whole of the world.

I believe in reason, evidence and the human mind,
the only tools we have;
they are the product of natural forces
in a majestic but impersonal universe,
grander and richer than we can imagine,
a source of endless opportunities for discovery.

I believe in the power of doubt;
I do not seek out reassurances,
but embrace the question,
and strive to challenge my own beliefs.

I accept human mortality.

We have but one life,
brief and full of struggle,
leavened with love and community,
learning and exploration,
beauty and the creation of
new life, new art, and new ideas.

I rejoice in this life that I have,
and in the grandeur of a world that preceded me,
and an earth that will abide without me.

(hat tip to Pharyngula)

Vetskeptics blog

A blog baby!
This little blog project at wanderingprimate has always been about pondering on a rather wide breath of topics. Hopefully regular readers- if any- have enjoyed some of these posts as I have meandered- or wandered- about from topics in physics, medicine and other science related themes that have caught my fancy. As long as it is enjoyable, I plan to continue writing and perhaps broaden the scope a bit- touching more on other sciences and philosophy from time to time.

Along the way, I have managed to build up a fairly significant body of veterinary posts that have proven useful and may be of some use to others. With that in mind, I’ve decided to create a new veterinary specific blog site -Vetskeptics- with the goal of collecting these posts into an easier to access format and, at the same time, initiate a veterinary specific site that promotes critical thinking and skepticism.

My goal is to add to the scarce resources on the "ether" net for veterinary skeptics, or any animal lover tired of the pseudo-scientific blather out there. I hope to improve on some of the old posts and have new authors send in their own quality posts in an effort to put together a more collaborative site of like minded veterinarians, veterinary technicians, animal care-givers or any animal lover interested in sharing their thoughts.

If nothing else, it will be a nice skeptical reference blog. If you are interested in helping out, please have a gander at the site and drop me a line at (drg at vetskeptics dot com).

It could be a lot of fun!

Prions: mysterious shape shifters

Everywhere and nowhere

It is the strangest thing to see a vibrant and healthy Colorado bred elk begin to shrivel and waste away before your eyes. It is even more frustrating to feel that old familiar tinge of complete helplessness when the realization comes to you that chronic wasting disease has taken (CWD) hold of another victim. No matter how aggressive and careful you are there is literally nothing that can be done once this mysterious disease takes hold.

Thankfully, the incidence of this prion based sickness is relatively rare and slow to ravage whole herds. This is good as the best we can do to control CWD is to monitor it by testing the tissues of captive adult animals that have died or researching “test and cull” methods for eradicating it from wild herds.

The mechanisms that make this disease so bizarre and counter intuitive starts with the causative agent – a prion- a small protein structure without any nucleic acid. They are described as “small proteinaceous infectious particles which resist inactivation by procedures that modify nucleic acids.”

This is indeed beyond strange. The idea that a protein structure by itself can cause disease defied a lot of what was known about infectious disease. The infected animals are usually neurological and the disease is now classified into a family of “spongiform encephalopathies” based on the post mortem lesions found in affected mammals¹- of which most seem to have some version of this thing (table 1). They are all characterized by varying degrees of loss of motor control, dementia, wasting (paralysis) and eventually death.

Table 1 some prion diseases:

• Scrapie: sheep
• TME (transmissible mink encephalopathy): mink
• CWD (chronic wasting disease): muledeer, elk
• BSE (bovine spongiform encephalopathy): cows
• CJD: Creutzfeld-Jacob Disease: human
• GSS: Gerstmann-Straussler-Scheinker syndrome: human
• FFI: Fatal familial Insomnia: human
• Kuru : human
• Alpers Syndrome: human

An interesting historical anecdote regarding early prion research is touched on by Dr Shaun Heaphy lecturer at the University of Leicester “Kuru is the condition which first brought prion diseases to prominence in the 1950s. Found in geographically isolated tribes in the Fore highlands of New Guinea. Established that ingesting brain tissue of dead relatives for religious reasons was likely to be the route of transmission. They ground up the brain into a pale grey soup, heated it and ate it. Clinically, the disease resembles CJD. Other tribes in the vicinity with same religious habit did not develop the disease. It is speculated that at some point in the past a tribe member developed CJD, and as brain tissue is highly infectious this allowed the disease to spread. Afflicted tribes were encouraged not to ingest brain tissue and the incidence of disease rapidly declined and is now almost unknown.” This rather macabre custom did illustrate how this strange infection behaved and how it might work through a population of people.

Even more intriguing, these prions seem to be related to a normal and abundant cellular protein (PrPc) located on the membrane on run of the mill neural cells. These prion like structures have a different structural shape than infectious prions and are perhaps functionally linked with normal neural transmission, though no one really knows for sure.

Prions and these PrPc proteins seem to have species specific structures but these configurations are fairly similar across the board. This species specificity dramatically slows down cross species infections and makes such jumps far less probable, but not impossible- especially if there is a susceptible individual on the other end.

The prion varies in its structural three dimensional forms from the normal PrPc protein and it’s this structural difference that seems to make them so insidiously pathological. To make matters worse, it seems there may be genetically susceptible individuals that are more prone to having their own PrPc proteins “shape shift” into the pathological infectious prion by coming into contact with a prion (by the way, not all shape shifted prions are lethal).

Interestingly, that it is possible to eventually “transform” an infectious prion from one species to another susceptible species is a prime example of witnessing evolution “unplugged” right before our eyes. The ability of these prions to evolve structurally and in time come up with the right configuration to cross species without any genetic elements is remarkable.

As ERV puts it “How does something with the same amino acid sequence evolve??”. With respect to prion research being done by Dr Bartz she adds “The idea I pitched to Dr. Bartz (the idea he was already planning on pitching to the scientific community hehe, I iz smrt) is that prions operate like HIV-1. But instead of exploring sequence space like my HIV, his prions explore structure space. One protein exploring all possible structural configurations. It has an optimal configuration for minks, but needs to explore and find a more optimal configuration for ferrets.” Amazing stuff!

What does a normal PrPc do? What makes its shapeshifted version so lethal? According to the Prion Institute “Studying how and why proteins misfold and the genetics, diagnoses and treatments of prion diseases will have positive implications for both animal and human health issues.”

Indeed, the possible breakthroughs for understanding the prion phenomenon may have staggering implications towards not just understanding the spongiform encephalopathies, but other degenerative neural diseases (i.e.; Alzheimer) as well as shed light on normal brain physiology. All this from a tiny inert blob of protein- reality is indeed far stranger than fiction.

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1) Visible end results at post-mortem are non-inflammatory lesions, vacuoles, amyloid protein deposits and astrogliosis.

Killing fields of Darfur, Chad and beyond

From people to endangered species: the travesty grows

The unending specters of misery and death so ubiquitous to the killing fields of Darfur have set their gaze to distant riches beyond the borders of Sudan. They have stirred and moved in the name of money on easy prey and this time it is the animals that suffer. According to Sharon Begley of Newsweek, the sad tale of this human travesty has now reached the world of Africa’s endangered species- and it’s killing them at near industrial scales.

As if a child’s dying cry wasn’t enough for the hungry hordes of the Janjaweed (nomadic proxies in a terrible struggle between Sudanese powers that be), they now spread their bloody reach into Chad’s Zakouma National park ; a refuge of endangered species and a tantalizing source of blood money for these killers. However, they aren’t the only "armies" in need of Chad’s treasures in a continent choked by desperation and greed. The endless quest to feed bloody struggles for power and domination can be seen in ever more brazen poacher raids like those supported by Somali warlords and demonstrate the perils of trying to defend the defenseless.

Once rebounding populations of elephants and rhinos among many other endangered species are now being decimated to fuel the ongoing human tragedy in Darfur, Somalia, and who knows where else. Begley notes that this “signals a terrifying turn in the world's efforts to save vanishing species. The battle is no longer just about the elephant's trumpet never again echoing over the African savanna, or the Bengal tiger's roar being heard only in memory. The threat posed by the contraband wildlife trade is now also about the money it generates—wave upon wave of it—that is being used by very bad people to do very bad things.”

Chadian park rangers are caught in the middle of a newer more vicious illegal animal trade whose endgame appears to be the very extinction of the animals they defend. The problem of course extends far beyond the borders of Sudan or Chad and reaches into the depths of India, Asia and North America. Part of the problem is the shear idiocy and ignorance of people who create a market demand for these animals in pieces and parts that end up as ivory statues or in "magical" aphrodisiac powders. By doing so, whether they know it or not, these buyers aid and abet in an unfolding human tragedy.

Begley concludes her article noting "that as the ultimate blame for drug lords who murder the innocent lies with users, so the blame for a wildlife trade that sustains organized crime and genocidal militias lies with the buyers. "There is a vague awareness in America that some things, they shouldn't be buying," says McMurray. "But the psychology seems to be that if it's in a store [or online] it must be OK." Americans who buy ivory carvings (easily available online), Japanese who collect the ivory signature seals called hankos and Chinese who clamor for "medicines" made from tiger bone are not supporting some lone poacher who's trying to feed his family. They're putting money into the coffers of the Janjaweed, warlords and possibly even worse actors. With the new wildlife traffickers, it's not only animals whose lives are at stake.”

Cry the children... and the animals….

Combating Malaria with mosquitoes

A possible novel strategy

There have been a lot of mixed results on the malaria control front. Simple and effective measures such as executing public malaria prevention campaigns, spraying against mosquito larvae, disseminating anti-malarial medications and mosquito netting have been slow to take hold due to a constellation of frustrating problems. The sad scourge of political corruption, extreme poverty and socio-cultural prejudice are but a few of the barriers that impede progress towards bringing down the death toll of this ancient protozoal disease that kills in the area of one million people a year.

This is why it is still worth perusing alternative strategies against the malaria parasite. Any measure that can help impact the effects of this disease should be considered and if found to be effective, added to the existing known strategies. This doesn’t include opening ones mind until your brains fall out and embracing implausible measures that just don’t work such as homeopathy and nutritional supplement “treatments”. Alternative efforts like these reflect -at best- a stunning dissonance between reality and belief or -at worst- complete and utter stupidity and a morbid disregard for human life.

However, among the more interesting possible anti-malarial strategies that might bypass some of the problems of other programs are biological approaches for combating malaria. For example, approaches that could cut its life cycle could dramatically reduce the prevalence of this parasite using a completely novel angle.

Actually, the idea itself isn't really new. Scientists have been trying for years to develop a malaria resistant mosquito that could survive in the wild. Until recently, the idea of combating malaria through biological mechanisms involving its life cycle has been a nice but impractical theory. It made sense but has been very difficult to make work- the devils been in the details. The good news is that recent developments in this area might breathe new life to this approach making it, at the very least, a promising avenue worth pursuing.

An interesting article in the January 2008 issue of Scientific American touches on some of the hopeful developments in this field. In summary, it mentions various lines of research on the malarial parasite life cycle, genetically engineered mosquitoes (Anopheles) and their capacity to survive in the wild that are coming together to perhaps create an viable and effective instrument for combating the malaria organism (Plasmodium falciparum).

In 2007, researchers found that the midgut environment of the anopheline mosquito, where the malaria parasite is transported and becomes infectious, plays an important role in the development of the malaria parasite. By genetically manipulating the mosquito to produce a substance found in Sea Cucmbers (CEL-111) in this midgut region, these researcher have been able to significantly inhibit the sporogenic development of Plasmodium falciparum.

The authors in this study note that “To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes.” These researchers basically have managed to create a viable mosquito resilient to the malaria parasite- an important piece of the puzzle.

Other threads of research are probing alternative mechanisms that alter the parasite life cycle within the mosquito and offer intriguing bits of information adding to the development of a robust data base for discovering more anti-malarial bio-mechanisms. For example, in the same year it was discovered that a capsule protein PbCap380 an ingredient of the malarial oocyst outer wall was critical for malarial survival inside the mosquito. The oocyst stage of the malarial life cycle is key to this parasites ability to infect humans and without this particular protein component the parasites were gradually eliminated from the mosquitoes reducing their capacity to transmit the disease.

Another study found they were able to reduce the adherence of the ookinate stage of the parasite to the lining of the mosquito midgut; an important part of eventual oocyst development by RNA interference. In essence they were able to reduce the level of a “ligand” – a glycoaminoglycans structure on the gut lining- that acts like Velcro.

Having a mechanism or mechanisms to inhibit plasmodium inside altered mosquitoes and maintaining a viable population of these insects are crucial steps toward a larger active bio-engineered anti-malarial program. However, one of the biggest steps in this area is to translate these successes to the field. If one or more of these mechanisms can be spread throughout the wild gene pool of mosquitoes then a whole new front against malaria could be established.

In fact, another recent study offers tantalizing evidence that transgenic malaria resistant mosquitoes can in fact survive in the wild. These authors note that “The introduction of genes that impair Plasmodium development into mosquito populations is a strategy being considered for malaria control. The effect of the transgene on mosquito fitness is a crucial parameter influencing the success of this approach.”

The study found that transgenicaly altered mosquitoes actually had a survival advantage in the lab when compared to non- transgenically altered mosquitoes. The authors conclude that the result of their findings “suggest that when feeding on Plasmodium-infected blood, transgenic malaria-resistant mosquitoes have a selective advantage over non-transgenic mosquitoes. This fitness advantage has important implications for devising malaria control strategies by means of genetic modification of mosquitoes.” On a related note, another important study in fruit flies reveals that it is possible to spread genetically modified insect genes in the wild.

Taken as a whole, one begins to see that several vital steps are being made to close the circle on a novel biological mechanism that can be used to reduce malaria in its natural environment. Each of these studies provides a brick of knowledge that begin to form a wall against malaria transmission. This fascinating activity may indeed be the genesis of a true “bio-weapon” against malaria and add to the greater effort in combating a deadly human disease.