Big shot names at the annual International AIDS Conference held last week in Vienna, which included philanthropists Bill Gates and Bill Clinton and numerous executive directors of UN health agencies, were treated to a presentation of some exciting new findings: the first ever evidence for biological intervention against HIV-I transmission. The intervention is in the form of a vaginal gel, which contains an anti-HIV drug that reduces the chances of infection by HIV by 39% (a statistically significant reduction). The 2 1/2 year trial consisted of more than 800 women, who were asked to insert the anti-HIV gel, or a placebo, within 12 hours before or after having sex.

This new line of defense against HIV comes at the heels of two other recent major findings of preventative measures against infection. The first is behavioral: school girls and their families receiving small monthly cash payments from researchers had sex later, less often, and with fewer partners. 1 1/2 years after initiation of the payments, girls were less than half as likely to be infected with AIDS. It seems the payments, small as they were, were enough to alleviate the need for girls to have sex in exchange for cash or presents. The second preventative measure found a few years ago was physiological: circumcised men were half as likely to contract HIV. What made that story particularly successful was that many men flocked to hospitals for the procedure because of another motivation: they heard that it made sex better.

The vaginal gel results are exciting because it is the first to unambiguously lay out a medical plan of action for HIV prevention. Prior to this, more than 30 studies of microbicides, vaccines, and drugs had failed, or provided only marginal success. So this is a big step!

As I’ve noted before, our bodies are riddled with microbes – there are more of them than there are of us (if you go by shear number). But where do they come from? Each individual has a complex ecosystem of commensal (harmless) microbes that live on our skin, in our nose, mouth, ears and gut, and we lay the foundations for this ecosystem at birth. According to a new study in the Proceedings of the National Accademy of Sciences (PNAS), different methods of birth (traditional vs cesarean section) have very different outcomes in terms of what bacteria end up colonizing you:

The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate’s first microbiota[…] We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother’s vaginal microbiota, dominated by Lactobacillus, Prevotella,or Sneathia, and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium.

It’s been known for a long time that c-section babies were more prone to allergies and asthma, and there’s a strong link between commensals and the immune system, but exactly what the difference was remained obscure. Basically, what this paper shows is that the types of bacteria that get us started are established very early.

Babies born through the traditional route are very quickly exposes to the bacterial communities of their mothers – both vaginal and gut bacteria (women often defecate when giving birth). Once these bacteria get established, they fill up all the niches, and prevent other bacteria from getting a foothold. By contrast, c-section babies don’t have this initial exposure – the womb is fairly sterile, and the conditions of this surgery prevent contact with the mother’s other mucosal surfaces. Because of this, the infant is ripe for colonization from the myriad of bacteria found everywhere else, from the nurses and doctors that handle them to the bacteria on the skin on the mother’s breast when feeding.

It’s important to note that we can’t yet draw a distinct causative link between early establishment of bacterial communities and future disease (allergies, asthma etc), right now it’s just correlation. And though infants are colonized by very few types of microbes, as they develop, the microbial ecosystem diversifies into thousands or millions of different species. Researchers are hard at work using new technologies to try to figure out all the different things living in an adult gut (given the spiffy name, “the microbiome”), and we’ve barely scratched the surface.

The one thing that is clear is that the little things living in us and on us can have a profound effect on our health, and with new research, hopefully we can use that knowledge to our advantage.

There’s a great article at Gizmodo about attempts to find new antibiotics by tapping into the local knowledge of healers in the rain forests of Belize:

It grows wild along the shores of the New River, among the Mayan ruins of Lamanai, next to the lilies that are home to little yellow birds that skip across the pads. Inside Belizean plants used for generations by native healers, a suite of chemicals produce a natural “anti-quorum sensing” effect that interrupts bacteria’s ability to communicate. And bacteria that can’t communicate don’t go pathogenically virulent.

At least that’s the hope. If they’re right, they’ve discovered the herbal equivalent of Neosporin.

Quorum sensing by bacteria is a hot new field of research, as disrupting bacteria’s ability to communicate may be an incredibly efficient way to prevent their adverse effects. The article also describes the sometimes eccentric head of the company (McAfee of computer anti-virus fame), and some of the political and scientific barriers to research of this type. The article is quite long, and it’s a bit sparse on the actual science, but it’s well worth the read.

(Note: This post is not for the squeamish)

All kinds of stuff lives in our guts. It’s been estimated that there are about ten times as many bacteria cells (microflora) in our body as human cells. Most of them are totally harmless, and indeed, they are often beneficial. But as the authors of a paper last week in Science pointed out, bacteria aren’t the only things living down there, and the beasties that live in our gut don’t always play nice, at least, not with us:

The inhabitants of the mammalian gut are not always relatively benign commensal bacteria but may also include larger and more parasitic organisms, such as worms and protozoa. At some level, all these organisms are capable of interacting with each other. We found that successful establishment of the chronically infecting parasitic nematode Trichuris muris in the large intestine of mice is dependent on microflora and coincident with modulation of the host immune response.

Trichuris is a genus of helminth worms that live in the large intestines of mammals. They are wildly successful; over 1 billion (yes, Billion) people are estimated to be infected with T. trichiuria every year. Infection starts with ingesting Trichuris eggs with your food. The eggs are able to survive the harsh environment of your stomach and make their way down to the large intestine, where they hatch and begin feeding, mating, and laying new eggs. When you defecate (we just can’t get away from poo on this blog evidently), the eggs are free to contaminate other food. If you read between the lines correctly, this means that at the beginning of the life-cycle, you must have eaten food contaminated with fecal matter (there’s a reason that this parasite doesn’t do well in regions of the world with good sanitation). This is not nearly as gross as the life-cycle of hook-worms, which can burrow into your foot, swim through your blood-stream to your lungs, then wriggle their way into your mouth through your trachea to be swallowed while you sleep – but I digress.

These researchers wondered what would trigger these ingested Trichuris eggs to hatch. If the worms hatch before they get ingested, they’ll die before they get there, and if they hatch too late, they’ll be expelled before they can establish themselves in the gut. So what is there a lot of in the location they want to hatch, that could provide a signal? Bacteria! When the researchers dumped all kinds of different bacteria on the worm eggs, they hatched. In addition, if they treated mice with high-doses of antibiotics to clear out their guts, and then fed them worm eggs, the worms didn’t hatch. Crucially, dumping bacteria on the eggs only worked if they were at body temperature (37 degrees C); at room temperature, it didn’t work. This makes sense from the worm’s perspective too – there are bacteria everywhere (especially in the poo they’re originally expelled in), but the only place there is likely to be lots of bacteria at 37 degrees is in a mammalian gut.

This doesn’t mean that we should go treating everyone in the 3rd world with antibiotics to prevent worm infections – the normal bacterial flora are too important. But it does raise some potential new lines of preventative therapy. While the exact nature of the interactions between worm egg and bacteria were not complete worked out, they did find that interactions with some types of bacteria were dependent upon a certain class of adhesion molecules, and that these interactions could be blocked by mannose. More understanding of how these different inhabitants of our intestines communicate at the molecular level will doubtless lead to great therapies, but as most of these infections happen in the third world, those therapies will have to be cheap if they’re to do any good.

A recent paper published online in the Proceedings of the Royal Society B (I have no idea what the B means, but maybe one of you can clarify with a comment) draws an enticing connection between whale excrement and climate change.  Because this study involved whale poop, it even made the mainstream news.  The folks at MSN were even nice enough to provide an areal photo of what it looks like when a whale goes to the bathroom.  I have been lucky enough to experience this first hand on a whale watch when a whale shared the contents of its bowels with those of us aboard the ship, so this study had a little bit of a personal connection for me!  Hat tip to Chrissy at Working Through the Blue for pointing me towards this article.

The paper (entitled “Iron defecation by sperm whales stimulates carbon export in the Southern Ocean”) can be found here, and seems to be available for download without subscription.  You might be wondering whether this study draws a connection to the microbial world, or if I am just excited to write about whale poop… I assure you there is a connection.  In most environments certain nutrients are limiting, and therefore control the rate of primary production.  This means that no matter how much energy (food, sunlight, or chemical energy) is available, the microbes that form the base of the food pyramid can only convert that energy into biomass (storing carbon in the process) when that limiting nutrient is present.  In the case of the Southern Ocean, iron is the limiting nutrient.  The microscopic phytoplankton floating at the surface take CO2 out of the atmosphere and convert it to biomass that eventually falls through the water column and acts as food for other organisms.  However, they are restricted in how fast they do this because there is not much iron dissolved in these surface waters.

This is where the Sperm Whales come in.  These giants descend into the cold dark depths to feed (mostly on squid), and come up to the surface to breathe and relieve themselves.  It turns out that their waste is iron-rich.  By depositing this lovely substance in the photic zone, they apparently stimulate primary productivity.  This means that the photosynthetic plankton absorb CO2, grow, reproduce, are eaten, and so on, and eventually organic material sinks down and provides energy to life in the darker regions.  But wait you say (being the savvy reader that you are), don’t the whales exhale a lot of CO2 back into the atmosphere?  Yes, they do, but according to the modeling of these researchers, the plankton take up much more CO2 as a result of the iron released by the whale than the whale releases.  “By enhancing new primary production, the populations of 12,000 sperm whales in the Southern Ocean act as a carbon sunk, remivong 2 x 105 tonnes more carbon from the atmosphere than they add during respiration”.  They go on to suggest that the reduction of whale populations due to whaling is likely to have diminished this carbon sink.

How did the scientists calculate all of this?  They first assume that these whales eat only cephalopods (mostly squid).  I do not study whales, so I don’t really know how accurate of an assumption this is, but it seems to be true for this region (in other areas sperm whales eat more fish).  Then, they used published reports of the amount of iron in cephalopods, and then calculated the amount of prey consumed by the whales by averaging previous studies that had estimated how much these animals eat.  From what is known about iron retention in marine mammals (maybe as low as 10%, they used 15% as their estimate), they were then able to estimate how much iron must be released by the whales during defecation.  They then had to figure out how much of that iron stays in the photic zone long enough to initiate primary production.  They did this by assuming (based on observations) that undigested squid beaks sink almost immediately, but that the liquid material stays around for a long time (this is admittedly non-quantitative).  Finally, they know the form that iron is generally found in the gut (ferrous salts), and they know that that form  can be expected to dissolve quickly and therefore would hang around in the photic zone.  Their estimate was that 75% of the defecated iron would stay around in the photic zone.

I explain this because while headlines like “whale poop may help offset CO2 emissions” are certainly catchy, to gauge the accuracy of this claim it is important to know how the numbers were crunched.  Flashy findings like this can trickle into the mainstream news, but people generally don’t get an explanation of why they should believe this.  [SoapBoxAlert] I think this is part of why it can be so hard for non-scientists to determine which bits of “science” to “believe” and which to be critical of, especially when it comes to climate change [now back to the regularly scheduled science].

In this case the researchers have made some very interesting calculations (they also provide estimates of the losses in carbon sequestration that historical whaling may have caused).  I think it is important to know that their numbers are based on a model rather than actual measurements of the iron concentration of whale feces or what happens to that iron over time.  Models are only as good as the data that go into making them, and in this case it seems (to me, admittedly knowing very little about whales) that they have done a pretty good job.  Whales are very difficult animals to study, and something as simple as sampling their feces would take much more time, energy, and money than you might thing, so I am certainly not faulting the authors for this.  Similar calculations were done to estimate the rate of carbon withdrawn from the atmosphere, and then sunk, but since this is already getting long, I will spare you those details.

In summary, this study provided me the opportunity to write about whales, poo, microbes, the carbon cycle, and scientific methods at once… what better way to spend a Sunday morning!

Although I studied physics and chemistry in college, I have always held an inherent appreciation for how life works.  And now, researching microbes in action, I am continually amazed by their diverse habitats and metabolisms.  It is remarkable to think how despite the diminutive size of microbes, they are dominant members of our biosphere and play a key role in every known biogeochemical cycle.  This list includes carbon, sulfur, nitrogen, and oxygen as well as trace metals such as iron, cobalt and zinc.  I have started thinking that if there is an available compound on Earth, then microbes have found a way to use it.

What does it mean that microbes are involved in these biogeochemical cycles?  It usually implies that a microbial species has found a way to use a form of that specific element while the microbe undergoes cellular respiration.  Although respiration is complex, I tend to think of it in a simplified manner as a transport of electrons from one compound to another by a living organism.  The organism utilizes this electron transport to produce energy in order for it to stay alive and reproduce.  As humans, we take electrons from the carbon compounds we consume as food and transport those electrons to the oxygen we breathe.  Since we use oxygen, this is aerobic respiration. One can think of the food we eat as electron donors and oxygen as the electron acceptor.  Now, a fascinating aspect about microbes is that different species have evolved to use a variety of electron donors and acceptors in respiration process.  Not only is this how microbes are involved in Earth’s biogeochemical cycles, but this is why certain microbes can be found in such extreme conditions, such as hydrothermal vents which have been discussed earlier.

Since microbes can use a variety of compounds as electron acceptors, what if there was a way to harness these electrons to produce electricity?  In 1911, M.C. Potter was reported to be the first person to observe electricity production from microbes but it has only been within the past 30 years that this research has gained momentum.  In these systems, which are called microbial fuel cells, the material the microbes are using as an electron acceptor is called an electrode, more specifically an anode. By connecting the anode with a metal wire to a region with even higher electron affinity, termed a cathode, we can generate a circuit.  Oxygen is one of the best electron acceptors and typically these systems have oxygen present near the cathode and the microbes grow in an chamber without oxygen in order for electrons to flow from the anode to the cathode.

Personally, I find the mechanism for microbes to transport electrons to a solid surface fascinating as a basic science question and think that understanding this process better would shed some light on how microbes do this in nature.  Right now, there are a handful of microbes known to utilize a solid surface as an electron acceptor and I am curious about what others are out there that have not yet been identified.  What do these different species have in common?  What influences growth and thus electron generation?  How is the structure of the microbes growing on the anode as a biofilm influenced by the anode properties, such as material composition or surface patterning?  How does the internal properties within the biofilm correspond to electron generation, such as pH?  To address these questions, I perceive microbial fuel cells as a useful system to explore how microbes form biofilms on surfaces that act as an electron acceptor.

Further, as a new area of research with potentially huge contributions to be made more knowledge will improve how this mechanism is utilized in technology not only for energy production but also for organic waste removal.  An attractive aspect of this technology is that electricity generation by the microbes goes hand-in-hand with organic waste removal because the microbes use the organic compounds as their electron donors, or food.  In wastewater treatment, this would allow for the water to become purified at the same time electricity is generated.  Electricity production is still quite low with one report stating that their microbial fuel cell design could power 16 60-watt light bulbs.  There is still room for improvement in power generation and I believe that addressing the mechanistic questions about microbial electron transport to an outside electron acceptor will aid in both improving our basis for building these technologies and our understanding of how our microbes are major players in our world’s biogeochemical cycles.

As I wrote earlier, scientists have a bit of a PR problem in communicating their science to the public. In the most recent issue of Nature, Naomi Oreskes and Erick Conway highlight the problem with respect to climate change (sorry, it’s behind a paywall, but I will quote them at length):

[…] opinion polls have repeatedly shown that large numbers of US citizens — and many in Canada, Australia and some parts of Europe — disbelieve the scientific conclusions. A December 2009 Angus Reid poll found that only 44% of Americans agreed that “global warming is a fact and is mostly caused by emissions from vehicles and industrial facilities”. There has been essentially no change in public acceptance of the scientific conclusions since the 1980s, with the public continually muddling the facts — believing, for example, that the ozone hole is the main cause of climate change.

In a recent book, these same authors showed how much of this public doubt was sewn in the later part of the 20th century by a few right-wing scientists who also worked to obscure the connection between tobacco and cancer and between CFC’s and ozone depletion.

What is particularly important to understand is how the industry used the trappings of science to make its case. It created the Council for Tobacco Research (originally the Tobacco Industry Research Council, but it dropped ‘industry’ on advice from a public-relations firm), along with various newsletters, journals and institutes, to publish claims. And it recruited scientists to speak up for this work, because it was obvious that tobacco-industry executives would lack credibility — although often the scientists had little or no expertise in medicine, oncology or epidemiology.

This strategy of creating a ‘scientific Potemkin village’ was applied to global warming too. During the period that we scrutinize in our book, the Marshall Institute didn’t create its own journal, but it did produce reports with the trappings of scientific argument — such as graphs, charts and references — that were not published in the independent peer-reviewed literature. At least one of these reports — read and taken seriously by the administration of former US president George H. W. Bush — misrepresented the science by presenting only part of the story. NASA climate modeller James Hansen and his team had demonstrated in the peer-reviewed literature that historic temperature records could be best explained by a combination of solar irradiance, volcanic dust, and anthropogenic greenhouse gases. The Marshall Institute report included only a single piece of Hansen’s graph, using the fragment to make it seem as if there was a poor link between carbon dioxide and climate warming, and to argue — against Hansen’s analysis — that the real culprit was the Sun.

Of greatest interest to me, however, was the identification of several of the problems scientists have in combating this type of approach.

One reason that the public is confused is that people have been trying to confuse them, in large part by intentionally waging campaigns of doubt against climate science. Doubt-mongering is an old strategy. It works because if people think the science is contentious, they are unlikely to support public policies that rely on that science[…]

[Those scientists] who engage in discussion discover a frustrating situation. Whatever facts one supplies, the sceptics continue to challenge them or offer alternative explanations. One cannot call one’s opponent a liar because it just seems desperate and ad hominem. Nor does it work to debate their points, because that feeds into the ‘controversy’ framework: the sceptics say there is a debate, you say there isn’t — voilà, they have proved their point.

The authors also point out some suggestions, some of which I agree with whole-heartedly, and others that are a bit more complicated:

For too long, the scientific community has subscribed to the idea that the ‘real work’ of science takes place in the lab or in the field, and that taking the time to communicate broadly doesn’t count. This assumption needs to be rethought, and the academic reward systems changed to encourage outreach. Contrarians do take the time and, given their tiny numbers, have had an enormous effect. In the nineteenth and early twentieth centuries it was much more common for scientists to write books aimed at the educated public; this tradition could be revived.

No argument here. Right now, tenure, promotion and pay grade at large research universities are largely based on grants and peer-reviewed publications. Having a few positions that are dedicated to public outreach, and are based on popular science publications and community education would be invaluble.

Scientists have much to learn about making their messages clearer. Honesty and objectivity are cardinal values in science, which leads scientists to be admirably frank about the ambiguities and uncertainties in their enterprise. But these values also frequently lead scientists to begin with caveats — outlining what they don’t know before proceeding to what they do — a classic example of what journalists call ‘burying the lead’.

A few weeks ago, 255 members of the US National Academy of Sciences wrote a letter in response to recent attacks on climate scientists. The Academicians began by noting that “science never absolutely proves anything”, and went on to explain that “when some conclusions have been thoroughly and deeply tested, questioned, and examined, they gain the status of ‘well-established theories’ and are often spoken of as ‘facts’”. Although this care and nuance is intellectually scrupulous and admirable, being so philosophical about the ‘factual’ nature of climate change doesn’t serve public communication.

This reminds me of the “just a theory” argument of evolution-deniers. The way that scientists use the word “theory” and the way that scientists use the word “theory” are drastically different, and this was deliberately used by the opposition to obscure the solid state of the fact of evolution. As a scientist, I do have qualms about over-stating certainty, but at the same time, I recognize that we need to speak differently to a general audience than we do with our scientific peers. I don’t mean talking down to the public, but rather changing our vocabulary so that we’re actually communicating what we intend to communicate.

The authors also make several other good points about scientists knowing their history and journalists stating their sources (often the “experts” on the anti-science side are scientists but in completely unrelated fields), but unfortunately, these are suggestions for when we’re called to debate, which is something we want to avoid anyway.

The article ends on a simultaneously optimistic and ominous note, and I’ll leave you with that

Of the many cases of doubt-mongering that we have studied, most ended for the better. At a certain point, the companies manufacturing chlorofluorocarbons (CFCs), admitted their link to ozone depletion and did the right thing by committing to phasing them out. The public is now firmly convinced of the link between cigarettes and cancer. Inductive reasoning implies that the same should happen with climate change: the consensus scientific view will eventually win public opinion. But in the meantime irreversible damage is being done — to the planet, and to the credibility of science.

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