Friday, November 30, 2012

All-Purpose Parasites: Why Parasites May Be The Next Miracle Drug

A long-term sufferer of Crohn’s disease makes yet another visit to his doctor, desperate to alleviate the symptoms he has been plagued by for so long. The patient has already undergone several surgeries to remove the portions of his intestine which were extensively damaged as a result of the disease, and can no longer work as the painful disease-related flare-ups have been increasing in frequency and intensity. The patient tells his doctor that he is desperate for relief and willing to try anything. After hearing this, the doctor considers the patient’s plea for a moment before handing him a prescription for parasites. The patient gratefully accepts the prescription and heads to the pharmacy, hoping that this will finally be the cure that he so badly needs.

Such a scene may seem unlikely, but it is already becoming a reality. The use of parasites in treating medical conditions at first seems counterintuitive, as they are primarily associated with their pathogenic qualities; however, a growing body of evidence indicates that parasite infection may be one of the most effective treatments for autoimmune diseases and allergies. For most people the idea of willingly infecting themselves with parasites may seem abhorrent, but for the millions of people who have suffered for years from painful and sometimes life-threatening autoimmune diseases and allergies, the choice is a no-brainer.

Our ancestors spent thousands of years evolving among a greater diversity of bacteria and parasites than we are accustomed to today. Parasite and bacterial infections were ubiquitous in Paleolithic times, and it wasn’t until the 1900s as industrialized urban cities began cropping up in developing countries that sanitation became a priority. Prior to improved sanitation, infectious diseases ravaged many communities and claimed thousands of lives. Most developed countries, therefore, tend to be intensely ‘germ-phobic’. The mere mention of bacteria and parasites makes most people shudder. In recent years, however, some of the stigma associated with certain bacteria and parasites has been reduced. It seems that being too clean has its own drawbacks, and now people in developed countries find themselves facing ailments which were unheard of prior to industrialization.

It is only within the past century that the incidence of allergies and autoimmune diseases has begun skyrocketing, an increase which is seen almost exclusively in developed or developing countries. Wealthy, industrialized countries have lower rates of parasite infection and yet have significantly higher rates of autoimmune diseases and allergies. While genetics seems to play a role in the development of these conditions, it does not adequately explain the disproportionate increase in autoimmune disease and allergies.

It has been demonstrated that environment also has a significant impact on our immune systems. Compared to most developing countries, industrialized countries are much ‘cleaner’- sanitation is more stringent, the citizens tend to be more informed about good hygiene, and the threat of infectious disease- including parasites- is minimal. Scientists are beginning to question, however, whether there is such a thing as being too clean.

In almost all developing or third-world countries, allergies and autoimmune diseases are practically nonexistent. Autoimmune diseases such as Type 1 Diabetes and Multiple Sclerosis, rare in African and certain Asian populations, increase when these populations migrate to a more industrialized environment, according to data from the World Health Organization (WHO). This effect is underlined by research conducted using mice as a model for Type 1 Diabetes. Non-Obese Diabetic (NOD) mice spontaneously develop symptoms mimicking Type 1 Diabetes in humans. Researchers have demonstrated that the onset and frequency of Type 1 Diabetes in NOD mice increased in mice raised in a controlled and sterile environment, while onset of diabetes symptoms is prevented in mice infected with parasites or a virus which affects the immune system in a similar manner.

While Type 1 Diabetes is only one example of an autoimmune disease which has become prevalent in modern society, similar effects have been observed in a surprising number of different diseases related to a malfunctioning immune system. Proponents of parasite therapy contend that the inverse correlation between parasite infections and the incidence of autoimmune diseases and allergies is in part explained by the ‘hygiene hypothesis’- in short, people in the United States and other highly developed countries are simply too clean, and haven’t had enough exposure to ‘germs’ and parasites. The foundation for the hygiene hypothesis was laid out by David Strachan in a 1989 paper published in the British Medical Journal on an epidemiological study of hay fever among British children that he had conducted for a length of 23 years. In the conclusion of the paper Strachan wrote of his observations that “allergic diseases [could be] prevented by infection in early childhood” and that “later infection or reinfection…might confer additional protection against hay fever”.

            Part of the ‘hygiene hypothesis’ maintains that throughout evolution, the immune system has been primed to remain at a baseline level of activity in response to a constant assault by bacteria, parasites, and viruses. Our immune systems, moreover, have evolved to become accustomed to infection by parasites and other invaders. In the absence of the appropriate immune challenges and itching for a fight, our immune systems begin attacking harmless substances (dust, peanuts, soybeans), or even our own bodies.

Ideally, our immune systems should function like a well-trained army: when a threat is perceived, the soldiers are given their instructions and advance an elegantly orchestrated attack against the invader. After the battle has been won, the soldiers- white blood cells and other immune system mediators- cease fighting, return to their barracks, and peace is restored. In autoimmune diseases and allergies, however, the soldiers ignore the cue to stop fighting, and initiate attack even in the absence of a threat. Normally the soldiers are trained to differentiate between the ‘enemy’ and their own forces; in autoimmune diseases, however, our bodies are assaulted by friendly fire from our own immune systems.

Parasites are one such target of the immune system. For thousands of years, however, parasites have been a part of the lives of modern humans- literally- and so the ‘Old Friends’ hypothesis refines the hygiene hypothesis through an added caveat. According to the old friends hypothesis, humans evolved alongside particularly abundant but harmless bacteria and parasites, and so our immune systems were trained to ignore otherwise harmless invaders because there were simply so many. Fighting off non-threatening microorganisms was a waste of time, energy, and resources for our immune systems.

Just like many young children sent off to school quickly learn to socialize and ‘play nice’ with their peers, the old friends hypothesis claims that our immune systems have also learned to be tolerant of certain microorganisms. Young children quickly learn that if you ignore the taunts of the playground bully, their antagonizer is often rendered harmless; after frequent invasion by certain abundant bacteria or large parasites our immune systems also learned that it just wasn’t worth the time and energy to fight off the invaders as long as they weren’t creating too much trouble within our bodies. As strange as it sounds, parasite and bacterial infections may be necessary for the proper development of our immune systems. Without the proper ‘training’ early on, our immune systems are not learning how to regulate themselves properly.

In the same way that humans have evolved and adapted to frequent invasion by parasites, parasites have also adapted to live with humans. Many parasites manage to avoid the threat of immune attack when colonizing humans because they have developed the means to evade the surveillance of the immune system and attenuate the immune response so that they can live and reproduce in peace within their host organism. This is primarily accomplished in two ways: first, parasites activate the regulatory T cells which normally keep the immune system in check. When regulatory T cells are activated, they prevent the immune system from mounting an immune response. Next, parasites act on the cells which normally initiate the inflammatory response to foreign objects. The use of parasites for therapeutic purposes exploits these qualities: not only do the parasites minimize the activity of the immune system, but when detected most of the immune system’s resources are directed towards fighting off the invading parasites, relieving the immune system’s attack on the body’s own tissues and organs.

In a recent article published in the journal Nature, Joel Weinstock, a pioneer of helminth therapy, refers to the evolutionary dynamic between parasites and their human hosts as being essential to shaping our immune systems and explains that “the evil properties of intestinal parasites are often overblown…. clearly, after thousands of years of co-evolution, the human immune system has evolved to handle the presence of most parasitic worms, which have, in turn, developed adaptations that enable them to live for years in a human host”.

In the article, Weinstock describes a flight to a grant-review session at the Crohn’s and Colitis Foundation of America as being a pivotal moment in his scientific career. At that point he was familiar with the hygiene hypothesis, and had previously conducted research on parasites. He also knew that parasite infection rates tended to inversely correlate with the incidence of autoimmune diseases in certain populations. When Weinstock first began speculating that parasites may have a therapeutic effect on patients with autoimmune diseases, he conducted preliminary research using mice with symptoms mimicking inflammatory bowel disease in humans. Administering parasites to the afflicted mice, he found, protected them from the disease, as he had predicted. Weinstock and his team were subsequently granted approval to test the parasite therapy in a single Crohn’s patient. The patient’s symptoms improved for several months after being given parasite eggs, without any adverse side effects. When the pilot study was declared successful, the medical testing eventually expanded to include 29 additional Crohn’s patients. The trial was an overwhelming success- nearly 80% of the Crohn’s patients exhibited a significant decrease in the severity of their symptoms, and 72% of the patients tested went into remission, with no reported side effects. Similar positive results were seen in a trial of 54 patients with ulcerative colitis, with almost 43% showing significant improvement.

The efficacy of parasite therapy is not limited to autoimmune inflammatory bowel diseases, however. Parasite therapy shows promise in treating a wide range of inflammatory disorders. A growing faction of scientists and medical practitioners now believe that in some autistic patients chronic inflammation may be to blame for their symptoms. Several studies have reported finding evidence of increased active inflammation and inflammatory signaling molecules in the brains of autistic patients and the fluid surrounding the brain and spinal cord. Following the same logic as the use of parasites in treating autoimmune disorders and allergies, clinical trials using pig parasitic whipworms to treat adults with autism are already underway. The trials are preceded by one case in which the father of an autistic child started his child on a parasite therapy regimen which essentially reversed the child’s symptoms, including the disruptive behavior which was beginning to spiral out of control prior to the parasite treatment.

Parasite therapy has been steadily gaining credibility among scientists and medical professionals, and now it is also getting the attention of pharmaceutical and biotech companies. Coronado Biosciences, a US Biotech company, began clinical trials for their newest ‘drug’, TSO (Trichuris suis ova), in August. A dose of TSO is no more than pig whipworm eggs in saline solution, to be taken every two weeks or as often as patients are advised to do so by their doctors. A similar trial is being conducted simultaneously in Europe by Coronado’s German collaborators at Dr. Falk Pharma GmbH. Pig whipworms, a type of helminth, are the only parasites which have been approved for use in clinical trials and medical research in the United States. The human gut is a dead end for mature pig whipworms, therefore the risk of re-infection or transmission to other people is minimal. The helminthes are unable to reproduce in humans, and so after the whipworm eggs are swallowed they hatch and briefly colonize the intestine before dying off two months later. Like most drugs, the helminth egg capsules need to be taken repeatedly to maintain the benefits of the therapy and keep patients’ symptoms at bay.

Gaining approval for parasite treatment as a standardized medical therapy, however, is most likely a long way off. The clinical trials which are currently being conducted were put off for years pending approval, and they are only officially recognized as ‘safety’ trials to determine whether there any negative consequences of pig whipworm ingestion. The results seem promising, and to date no complications or side effects as a result of treatment with pig whipworms have been reported.

If the results of the current and upcoming clinical trials continue to be as positive as in previous studies, it will be only a matter of time before pharmacies routinely stock their shelves with parasite eggs. Now that their reputation has been getting a makeover in the medical community, parasites, the scourge of public health officials and epidemiologists, may turn out to be a blessing for the millions of people suffering from severe, life-threatening allergies and autoimmune diseases.

Tuesday, November 27, 2012

Here Comes The Sun....Are We Ready?

In the wake of Hurricane Sandy, millions of people were left without electricity for weeks as utility companies scrambled to repair downed wires and damaged transformers. Even before the storm made landfall, the storm's threat to our power distribution systems was apparent, but it was almost impossible to adequately prepare for the extent of the damage incurred as the storm passed. Widespread power losses persisted for several weeks afterwards. Now, weeks later, the states that were hit the hardest are still steeped in the recovery phase. The possibility remains, however, that another storm could hit at any time, one whose effects may be even more devastating. These invisible threats are the solar storms that are brewing ninety million miles away- and should one of these solar storms head towards the Earth, the damage may be catastrophic.

The sun is primarily a giant, gaseous nuclear reactor. The bulk of its mass comes from the hydrogen atoms in its core which undergo nuclear fusion reactions to generate helium atoms and tremendous amounts of heat and energy in the form of radiation. The outer layers of the sun, however, are primarily made of plasma, which is little more than clouds of charged particles carried along by magnetic fields. The magnetic fields themselves are the product of the movement of the charged particles, forming a giant, self-sustaining web of magnetic current.

The sun undergoes a cycle of fluctuations in its magnetic field approximately every eleven years, and its observed activity changes accordingly as a result of the shifting magnetic forces. Solar 'activity' is used broadly to describe solar wind, solar flares, the formation of solar prominences, and coronal mass ejections. Entry into the phase known as the solar maximum of the solar cycle is marked by a prolonged and heightened flurry of activity. Fluctuations in magnetic fields on and around the sun's surface are responsible for the observed increase in activity during solar maxima, as measured by the number of surface sunspots and the frequency of massive solar flares and prominences. At present we are at the peak of the solar maximum, meaning that the sun is at its most active in eleven years, and NASA has estimated that the peak will last until approximately Fall 2013. Compared to previous solar cycles, the sun's current cycle is relatively mild- the last time the solar peak activity was as low as it is now was over a century ago. Regardless, the sun's increased activity in the midst of the solar maximum poses a threat to our astronauts and the electrical systems, and satellites we are so reliant upon.

The double solar prominences that occured on Nov. 16th. Image credit: Steele Hill, SDO/NASA

In the image above, the glowing (and presumably very, very hot) red loops are made of plasma, a cloud of electrically charged helium and hydrogen atoms. Plasma is swept along with the tide of the sun's ever-changing magnetic fields until the massive web of magnetic forces becomes unstable and the  forcefully bursts outward, causing the plasma to be ejected from the sun's surface. The plasma 'loops' formed are known as solar prominences, and can reach up to hundreds of thousands of miles away from the sun. On November 16th two large solar prominences were spotted erupting, and NASA caught it all on video. Fortunately, the recently observed prominences were not directed towards the earth; otherwise, the results could have been disastrous.

The corona, visible in an image taken during an eclipse. Image credit:
Solar flares, another form of solar activity, are the product of a massive release of the sun's pent-up magnetic energy which causes the release of large amounts of radiation from the sun (according to NASA, the amount of energy released could power the entire earth for ten million years- and even then, that energy is only a fraction of the amount of energy that is released by the sun every second!). They appear as bright spots on the sun (thus the use of 'sunspots' as an indicator of the sun's activity). Solar flares and other surface activity can sometimes create what is known as a coronal mass ejection (CME).

A solar eruption (coronal mass ejection, CME) from June 2011.  Image credit: SDO/NASA

In a CME, charged particles, matter, and heat are carried along by the force of the plasma explosion and, if headed in the direction of the earth, can  interfere with the earth's electrical grids and satellites. First, the outermost atmosphere of the earth would be bombarded with radiation and ultraviolet light, potentially disrupting radio communication. The real trouble comes later- sometimes days after the actual CME event- when the CME cloud reaches the earth. The plasma cloud also hauls billions of tons of matter along with it, comparable to the weight of Mount Everest slamming into the earth. As solar charged particles enter the earth's atmosphere, many orbiting satellites would be at risk. Many of the charged particles will also be drawn into the transmission wires on electrical grids, overloading the wires and potentially damaging transformers as a result of the the surge of electricity. Many experts believe that the potential damage to our electric distribution systems could be so heavy that it would result in widespread and prolonged power outages and have a significant economic impact as a result.

In terms of solar storms, size isn't all that matters- even a relatively small solar storm could be disastrous if it reaches the earth. It already happened once in 1859, in the midst of a solar maximum comparable to the cycle we are in now, according to NASA. Now known as the 'Carrington Event', named for the man who first realized the connection between solar activity and accompanying disturbances on earth, it was one of the worst solar storms ever encountered. As a surge of solar particles collided with gases in the earth's atmosphere, the 'northern lights' were visible as far south as the equator. The mass entry of charged solar particles into telegraph wires caused several telegraph stations to explode and damaged telegraph wires. The modern electric grid is still vulnerable to geomagnetic disturbances such as the 1859 solar storm, and widespread power outages or damage to transformer and the electric transmission system would be far more damaging due to our heavy reliance on electrical power.

Regulatory agencies are beginning to recognize the danger of GMDs as we enter the solar maximum, and have begun addressing the vulnerabilities in our electric distribution systems accordingly. After a careful review of professional testimony regarding the potential threat of geomagnetic disturbances (GMDs) such as solar storms, the Federal Energy Regulatory Commission (FERC) announced in October that it had found that "GMD vulnerabilities are not adequately addressed" in current standard operating procedures, "[constituting] a reliability gap" in our electrical grids. Based on these findings, FERC set forth a plan dictating that utility companies be prepared to address electrical failures as a result of GMDs and that preventive measures are put in place to protect electrical equipment from potential damage or failure after a GMD.

Scientists have also been paying more attention to the sun, carefully scrutinizing its activity to better understand the properties of the sun and the events which create solar storms. The Solar Dynamics Observatory at NASA is devoted to collecting information about the sun's activity in real time- fluctuations in the sun's magnetic fields, radiation emissions, the way the activity of the sun varies throughout the solar cycle- and analyze the information to look for patterns and make predictions about events which may affect the earth. According to their website, the SDO collects enough data to fill an entire data CD every 36 seconds!

Through the combined efforts of researchers, electricity distribution centers, and regulatory agencies, the susceptibility of our electric grids to solar storms is being addressed to protect some of our most valuable resources: energy distribution systems. Although we have never experienced a solar storm on earth of the same magnitude as the Carrington Event, many experts believe that there is a strong possibility we may one day find ourselves in a similar situation, in which case it is best to be prepared.

Picture of the Northern Lights taken near Norway in January of this year. The lights were visible farther south after a coronal mass ejection cloud reached the earth's atmosphere. Image credit: Ole C. Salomonsen

If you have the time, click here to go to the SDO's images page. There are some really great images of the sun in action in the gallery!

Tuesday, November 20, 2012

Is Scientific Misconduct More Prevalent Than We Think?

So I visited the blog Retraction Watch today for the first time (why write a blog on retractions? Read the author's explanation here), and was surprised at the frequency of fairly significant retractions/investigations into scientific publications. The authors themselves write in the FAQs that "although [they] didn’t predict this, it’s been a struggle to even keep up with retractions as they happen".

For those of you who haven't heard of Retraction Watch before, it is an independent undertaking by Adam Marcus and Ivan Oransky where they report on recent retractions or investigations into scientific misconduct, etc. of papers published in scientific journals in the life sciences.

Headlines included a professor having a seventh (!) paper retracted, many 'accidental' duplicate publications, the Moriguchi stem-cell transplant debunking, and a researcher who discovered that almost half of a paper that he had previously published had been plagiarized by a paper in the same journal where the original was published.

I wanted to include something substantial here because I haven't updated in a few days, but I think it would be appropriate to redirect you, dear reader, to a Science 2.0 article that I wrote two months ago when the PNAS article about scientific misconduct came out.

Read the full article here, and let me know what you think!

The original PNAS paper citation: Ferric C. Fang, R. Grant Steen, and Arturo Casadevall. Misconduct accounts for the majority of retracted scientific publications. PNAS 2012 ; published ahead of print October 1, 2012,doi:10.1073/pnas.1212247109

Thursday, November 15, 2012

This image of Drosophila ovaries was taken by Gunnar Newquist from the University of Nevada, and it came in 7th place in the 2011 Olympus BioScapes Digital Imaging Competition. The large red ovals are fully formed eggs, while the bluish structures below are 'chains' of developing eggs.

Every female fruit fly is equipped with a pair of ovaries which remain connected by a stalk (shown in green). The Drosophila ovary is a marvel of biological engineering: each ovary is made up of approximately 16 ovarioles which are set up in assembly line fashion. Stem cells residing at the tip of each ovariole divide to give rise to a single cell that subsequently undergoes four additional divisions. After it has completed these divisions a 16-celled 'cyst' is formed, with all 16 cells remaining connected. Only one cell will become the oocyte, or egg, while the remaining 15 are 'nurse' cells- they support and provide the developing oocyte with the nutrients it needs to grow as well as instructions for making certain proteins. Eventually the nurse cell contents fuse with the oocyte and a mature egg is formed. Each cyst is separated from other developing cysts by a single layer of cells and a short stalk, forming structures known as egg chambers.This entire process is repeated throughout the life of the female, and so each ovariole is really a string of egg chambers at different stages of development- the youngest cysts are closest to the stem cells, while the oldest cysts and eggs are clustered at the very end of the assembly line.

That's the simple explanation, at least, but throughout egg formation many processes are occuring simultaneously, and there is a lot of cross-talk between all of the different populations of cells within the ovary and between cysts. It is only through a massive concerted effort that each egg is formed with all of the necessary instructions laid out in preparation for creating a fully formed fruit fly larva after fertilization.

Wednesday, November 14, 2012

Navel-Gazing In The Name Of Science

Image credit: Belly Button Diversity
Navel gazing has apparently gained some legitimacy in the scientific community, as a group of scientists has begun cataloging bacteria from volunteers' belly buttons in an effort known as the Belly Button Biodiversity Project.

The project began when the team collected bacterial samples from 60 volunteers, handing out swabs at a conference and to visitors in a museum. Lurking within those 60 belly buttons were 2,368 different bacterial species, many of which have never been encountered by scientists before. Some of the results were bizarre- one science writer had a bacterial freeloader that has only ever been found in Japanese soil, although he had never been to Japan- and others somewhat unsettling, such as the volunteer carrying extremophile bacteria typically only found in ice caps and thermal vents.

The team is now expanding its efforts to collect swabs from hundreds of belly buttons to test the bacterial makeup of their volunteers' navels and look for correlations among the samples. Although no single species was found in every sample, a handful of species were overrepresented within the original 60 samples. Eight species in particular were found on over 70% of the subjects, and they tended to dominate the overall bacterial composition of the sample in which they were present. One enthusiastic researcher described our belly buttons as being "a lot like rainforests", where certain species always dominate the rainforest flora.

Microbes have been gaining popularity as scientists are beginning to realize the importance of the relationship between humans and our native bacterial populations. Not only do microbes cover virtually every exposed inch of our skin and orifices, but the type and variety of bacteria found on our bodies, as well as the proportions in which they are present, appears to be linked to our health and well being. Now, the Belly Button Diversity Project team has joined the increasingly widespread effort to tease apart the nature and intricacies of the relationship between us and our microscopic inhabitants. For something so tiny, these critters have thus far had a huge influence on the trajectory of science, health, and medicine.

Read the full National Geographic Article here.

Friday, November 9, 2012

When Parasites' Worlds Collide

In the world of parasites, sometimes the hunter becomes the hunted (or, perhaps more appropriately, the parasite becomes the parasitized).

As its name suggests, the life of a worker ant is all work and no play. Their time is solely devoted to tending to the queen, securing food for the colony, caring for their young, and defending the nest. As the worker ant scurries along well-traveled paths in the course of its daily routine, however, it may not discern the threat overhead: when the worker ant unknowingly picks up spores released from an overhanging 'zombie-ant fungus', the ant becomes infected with the 'zombifying' fungus. 

After infection the normally reliable and consistent worker ants begin to exhibit a number of unusual behaviors. They mindlessly depart from their usual routes, convulsing, stumbling, and wandering around aimlessly. Every fungal infection, however, ends with the same eerie ritual: right on cue, at high noon the infected ant sinks its jaws into the main vein of a leaf, orienting itself to the northwest and assuming a position where the fungus will have easy access to the soil below. At this stage of infection the ant already has a head swimming with fungal cells and nerve toxins which are presumably to blame for their strange, jerky movement, loss of balance, and convulsions. The muscles around the ant's mandibles have also begun atrophying, and so after the ant bites into the leaf it develops a case of 'lockjaw'. The ant's 'death grip' anchors its body in place, and even after the ant dies several hours later it remains unmoved. The carcass of the ant remains in place for several days as a fungal stalk grows inside of the head of the deceased ant, eventually emerging and spreading its own fungal spores to other unfortunate passing ants.

Image credit: Wikimedia Commons/David Hughes/Maj-Britt Pontoppidan/PLoS ONE

The "zombie-ant" fungus (formally known as Ophiocordyceps) has evolved to capitalize quite efficiently on all of its available resources. Ophiocordyceps propagates itself by targeting ants, the most abundant insects on earth, and uses them as vehicles for its reproduction and to facilitate its movement to new hosts.  In a 2011 BMC Ecology paper the authors cryptically explain that "while the manipulated individual may look like an ant, it represents a fungal genome expressing fungal behavior through the body of an ant"; in essence, the fungus takes control of the ant's body and exploits it for its own purposes. In its takeover of the ant, the fungus ensures that all conditions are optimal for its reproductive success. The 'zombie-ant fungus' appears to be a widespread phenomenon, as there is evidence that different fungal species are found across the globe, each specialized to target local ant species.

Had the infected ant remained within the confines of the colony, its body would have been quickly extricated and heaped upon other deceased ants in the colony's 'ant graveyard' before the fungus had a chance to grow and mature. Because the fungus appears quite unexpectedly, however, and its presence is unanticipated, unsuspecting worker ants are more prone to infection. As the fungal takeover of the ant proceeds, the unwitting host begins to stray outside of the colony, having been 'programmed' to do so by the invading fungus. The ant then wanders along the forest floor, far enough away from the colony that its carcass won't alarm the other workers, but close enough that other worker ants may pass by it in their travels. 

Image credit: The American Naturalist/ University of Chicago Press

All told, the 'zombie-ant' fungus (in all of its many specialized forms and species) has been quite successful. After it has taken over and effectively killed off its host, however, another fungal species threatens to parasitize the original fungal parasite, and in this way the host-parasite relationship comes full circle.

The second fungal parasite appears to grow specifically on the ant and 'zombifying fungus' stalk, while the surrounding environment remains largely unaffected. As the new fungus carpets the ant-fungus remnants, the original fungal parasite can no longer release its spores. It has been suggested that this ultimately works to the benefit of the first fungus- had its success gone unchecked, it could easily decimate an entire ant colony. Because the first fungus is slightly crippled by the second, however, a balance between the parasites and host colony is maintained. Parasites must be able to effectively and efficiently exploit their hosts to their own purposes, however, if the process is too efficient- if they kill off their hosts too soon, in some cases, or whittle down the population of potential hosts to a critically low level- then their efficiency can be a detriment to their own livelihood.

Mother nature works in mysterious ways, and so the host-parasite relationship is often supported by an intricate framework of checks and balances. And, as indicated by the previous blog post, parasites can come in all shapes and sizes. 

The takeaway? In a fungus-eat-(er, sterilize)-fungus world, there is never a clear biological 'winner'. 

"What's The Magic Word?" (And No, It's Not 'Please')

If you think you've got it bad studying for an upcoming exam, researchers found that young fairy wrens are also expected to learn- but these fairy wrens are learning while still in the egg. Should they fail to do so, they won't just be given a bad grade- instead, their mother may refuse to feed the hatchlings, or their parents may abandon them altogether.

A young fairy wren's next meal, it appears, is dependent on their retention of a song taught to them as an embryo. Sonia Kleindorfer, a researcher at Flinders University, initially began recording fairy wrens to identify anti-predator calls. While the wrens were being recorded, however, she noticed that fairy wren mothers were singing to their unhatched eggs. She also noted that after hatching the begging calls of fairy wren chicks matched the song their mothers had sung to them before hatching, and that the learned songs varied between nests. She eventually realized that the fairy wren mothers were teaching their offspring a unique note, or 'password', with the expectation that after hatching they will have retained that password and be able to reproduce that particular note. 

Typically, after fairy wren eggs hatch, the parents provide for their young by bringing food back to the nest. As the mother wren returns with dinner the nestlings clamor for food by chirping out begging calls. Before the female feeds the nestlings, however, they must repeat the same note which they were taught while still inside the egg, allowing the mother to identify the nestlings as her own. If the note goes unrecognized, the nest is abandoned and the nestlings are left to fend for themselves.

A superb fairy wren ('superb' isn't being used as an adjective here- the superb fairy wren is the species of fairy wren which Klinedorfer and her team were studying.) Image credit: Wikipedia

It's not that mama wren doesn't love her children; rather, the 'password' is an evolutionary adaptation to the threat of being parasitized by other birds. By teaching their embryonic offspring a unique learned note, fairy wren mothers ensure that they will not be tricked into caring for the hatchlings of other parasitic bird species. Fairy wrens in particular are prone to deceit by neighboring cuckoo birds. Parasitic cuckoo bird mothers often lay their eggs in a fairy wren's nest, liberating themselves from the responsibility of having to raise, feed, and care for their own offspring. Although they are similar in appearance, cuckoo bird eggs hatch before true fairy wren eggs, and the young cuckoo birds push the unhatched fairy wren eggs out of the embryo. The duped mother wren would then unknowingly give up her time, energy, and valuable resources in caring for the cuckoo bird's offspring if the deceit was never spotted.

A female cuckoo bird. Image credit: Animal Planet/

To confirm that the 'passwords' were learned and not genetic, Kleindorfer swapped the eggs of 22 nests with other fairy wren eggs before the embryos were 'taught' by their mothers. The  newly hatched fairy wrens mimicked the song of their foster mothers and not their biological mothers, indicating that the song had been learned by the embryo as a direct result of the adult's communication. There also appears to be a learning curve: when a fairy wren mother repeats her song more frequently, her offspring produce a better mimic of the song. Additionally, when Kleindorfer and her team played foreign begging calls at the nests, neither parent fed the fairy wren chicks.

 Even so, fairy wrens only retaliate against the duplicity of parasitic cuckoo birds by abandoning the nest approximately 40% of the time, a number which has varied throughout the years. While the 'password' method is far from perfect, it is a unique approach to counteracting the threat of cuckoo bird parasitism and implies that young fairy wrens are able to learn from their parents even as embryos. So even if you can't teach an old fairy wren new tricks it seems that you can teach a young embryo new songs, a feat which is far more impressive.

Monday, November 5, 2012

They May Not Win Any Beauty Contests, But They Both Won The Biological Lottery

What do naked mole rats and blind mole rats have in common?

Besides two-thirds of their name, that is- and the fact that you probably wouldn't want to find yourself next to a representative of either species in a dark underground tunnel.

A face only a mother could love. No, that's not an undercooked sausage, that's a naked mole rat. Image credit: Meghan Murphy, Smithsonian's National Zoo/File
Ditto: blind mole rat. Image credit: University of Rochester
The answer, surprisingly, is that as far as we know both species are resistant to cancer, the biological scourge of many complex multicellular organisms.

But the similarities end there. Even though the rodents are two peas in a loosely related evolutionary pod, the way in which cancer resistance is conferred differs between naked and blind mole rats.

Three years ago a team of researchers led by Vera Gorbunova at the University of Rochester linked naked mole rats' ability to evade the development of cancerous cells to the rodents' p16 gene. One of the hallmarks of cancerous tumors is that cancerous cells tend to literally overstep the cellular boundaries between themselves and their neighbors. When a normal cell bumps up against neighboring cells, that serves as its cue to cease any additional divisions in a phenomenon known as contact inhibition. Many cancerous cells, however, continue dividing regardless of the crowding in their immediate environment.

Mammalian cells will only tolerate so much crowding before reaching levels sufficient to activate contact inhibition. In naked mole rats, however, the cellular crowding tolerance level is much, much lower. Even at low-level crowding conditions the researchers found that the gene p16 was activated in the tunnel-dwelling rodents, stemming the overproliferation of cells earlier than in their murine (mouse) counterparts.

Since then Gorbunova and her team have extended their study to include blind mole rats, who seem to remain cancer-free along with their hairless, wrinkled cousins. Interestingly, they found that a second mechanism seems to be responsible for the blind mole rats' cancer resistance. After taking the rodent's cells and forcing them to divide beyond normal limits in a cell culture dish, they found that after 15-20 divisions all of the cells quickly died off. The mass cell suicide, they found, is triggered by a protein known as interferon beta which is secreted from the precancerous cells. In addition to committing 'cellular suicide' by being toxic to the original secreting cell, interferon beta also killed off other neighboring cells. The 'clean sweep' therefore eliminates both the precancerous cells and other potentially precancerous cells as a preventative measure.

Any increased understanding of the mechanisms by which cancer can develop or ways in which it can be combated are valuable tools in our medical arsenal in the fight against cancer, which is currently the second most common cause of death in the US. Despite their somewhat frightening appearance, these underground rodents are invaluable resources as models for the study of cancer mechanisms and natural defenses against cancer. They may not win be winning any beauty contests, but these tunnel-dwelling critters may be a beautiful opportunity for the advancement of the current state of cancer research.