Forget cockroaches.  Bacteria will be the only organisms left if we manage to launch a warhead too many or if any doomsday scenarios actually occur.  It's a good thing - without bacteria we wouldn't be alive.  Bacteria control nutrient cycles and help us make cheese, but they can also kill us (it should be noted that pathogenic bacteria make up a minuscule portion of the known bacteria).  Their astounding diversity has allowed them to become the earth's dominant life form.

Even our bodies are not our own.  The average person has five pounds of bacteria (1.2 kg) in their intestinal tracts and on their skin - and bacterial cells outnumber our own cells by a factor of 10 to 1.  This difference is more pronounced on the genetic level.  While the human genome encodes approximately 25,000 unique genes, the bacterial community in our intestines alone produces an astounding 9 million.  Some scientists have even proposed that the human is a "super-organism" and these bacteria play a major role in our health.  Scientists have postulated that bacteria may cause syndromes as diverse as irritable bowel syndrome, colon cancer, and yes, even autism. 

One major misconception is that bacteria are inferior or unevolved when compared to higher animals.  Although they may be simpler (in the context of size and structural complexity), bacteria have also spent the last 3.5 billion years evolving to inhabit niche habitats.  So a better way to think of bacteria is how we think of humans - perfectly adapted and at the pinnacle of evolution.  And they can survive conditions that we can't even imagine - I've isolated bacteria from hot springs so acidic that they can dissolve a cow within two weeks, and I've worked with bacteria that can eat methane and breathe sulfur.  If we find bacteria on other planets, it will probably be because we sent them there - even NASA clean rooms are not sterilized enough to kill every bacteria.

Even more astounding than the diversity we've discovered is the diversity that we can't discover - it is estimated that up to 99.99% of all bacterial species cannot be isolated in a pure culture using current technologies.  Imagine if 99.99% of birds were invisible, and you begin to see the problems that microbiologists face trying to catalog life's dominant form.  In a gram of soil there are as many as 10 billion bacterial cells - more than the Earth's human population.  Go to deep salt mines, oxygen-free caves filled with sulfuric acid, and the bottom of the ocean; look inside rocks, trees, your mouth, and nuclear waste dumps; in all of these places you'll find bacterial life.

While here at the MPI, we've tried to discover more information about a small subset of these soil bacteria, those that consume methane.  Although this order of bacteria was discovered in 1904, we still don't know very much about them.  For example, we know that they can consume atmospheric methane (23 times more potent as a greenhouse gas than carbon dioxide) but we're still not sure exactly how - the leading theory is that some bacteria contain an isozyme which allows them to consume methane at a lower concentration than cultured species, but we still have not detected this isozyme in nature.  On a more general note, we're not even sure what percentage of soil bacteria can consume methane, nor do we know how many types of methanotrophs there are.

As we discover more about microbial ecology, we realize how little we know - but also that these organisms determine many more aspects of our lives than we thought possible.  In the 18th and 19th centuries, scientists began to catalog life's macroscopic diversity, providing us with a good overview of how the environment is structured.  We are now beginning to discover life's microscopic diversity, and while bacteria may be less exciting than, say, tigers or lions, this knowledge will deepen our understanding of earth's fundamental ecological processes.  We will probably discover unexpected benefits along the way (how many pharmaceuticals were developed from plants?), but the most exciting aspect is its audacity.  At it's most basic level, we're extracting information from dirt and using it to understand the world around us.  How cool is that?

New research from Mitchell et al. (Nature, July 2009) seems to indicate that higher animals (i.e., those of us lucky enough to have a central nervous system) aren't the only ones able to prepare for the future based on current environmental conditions - bacteria (E. coli) and yeast (S. cerevisiae) can do it too.  While it seems odd, the basic principle has been recognized for years.  Indeed, the lac operon in E. coli activates the genes needed to digest the sugar lactose, but the lac operon is activated only by lactose.  This mechanism makes good sense from an evolutionary perspective - proteins are expensive to produce, and if the cell does not need them (i.e. there is no lactose to digest) then producing them is wasteful.  While direct links like this one are easy to uncover, more subtle ones have remained a mystery - until now.

The biggest misconception that we need to get rid as higher mammals is the concept of memory - bacteria are unicellular organisms, so there is quite literally no way for them to develop a nervous system (or even a single neuron!), so any response and regulation has to be encoded directly into their genome.  That's where the second misconception comes in - individual bacteria don't really matter, and since their doubling time is about one hour, the number of offspring that can be produced in a short amount of time is high - as is the corresponding number of mutations and selection pressure. 

Here's where we come to the experiment.  Imagine that every time an E. coli culture is exposed to lactose, exposure to glucose follows.  Over time, the bacteria whose genes encode for the appropriate regulatory response (every time you see lactose, make the enzymes needed to digest glucose) will have a significant survival advantage over those that don't.  Think Pavlov's dog - every time the bell rings, it was conditioned to salivate.  With E. coli, lactose is the bell and glucose enzyme production is the salivation. 

Why might this be useful?  E. coli and Homo sapiens (that's us!) have a long history (not just related to contaminated beef).  In fact, most E. coli strains are helpful and make it easier to digest food.  But they have to get into our intestines somehow, and that environment is variable.  The sugars present in the stomach (where the bacteria enter) are different from those present in the large intestine (where the bacteria spend a lot of time), so if the stomach sugars can prime the bacterial cells to digest the sugars found in the large intestine, they'll have an easier time surviving in the new environment. 

The most fascinating implication of this study is how old the conditioning pathway is.  Eukaryotes (everything ranging from amoebas to humans) split from the bacteria (and archaea!) about three billion years ago, and since this genetic conditioning response is found in both bacteria (E. coli) and yeast (eukaryote), it is likely that the age of the pathway predates both - so "planning" for the future (anthropomorphism is a bad idea at the unicellular level) may actually be one of the oldest complex processes that there is.

For the scientifically-minded, here's a link to the original article.  Sadly, it is not open-access.

Sixty days ago, a novel flu strain from Mexican pigs brought the world to a minor panic.  As the data started to come in, it looked as if the strain was a serious illness in young, healthy victims - the same pattern seen with the 1918 outbreak.  The initial mortality rate was just under 10%, a shockingly high figure, but after the first two weeks the rate had dropped down to 1%, mostly a result of more thorough testing of those with flu-like symptoms.  In that same time frame, pig farmers and the pork lobby fought to change the name from "swine flu" to "Influenza A (H1N1)", a change which the WHO adopted.  While it may seem a bit silly, the name change helped to reduce panic - think about how many warnings you got to avoid eating pork (which is just silly - cooking the pork would kill the virus, and even if you ate truckloads of infected raw pork, which I don't recommend, the viral particles are not going to survive the passage through the intestinal track.  Within three weeks, global coverage of H1N1 dropped to a trickle.  If the virus is mentioned today, it is usually in connection with the first death in a new country. 

Ironically, the situation has worsened since the 24-hour coverage stopped.  On June 11, 2009, the WHO declared a pandemic (a global epidemic).  While this sounds scary, it just means that spreading in more than one global region (and the way that they define global regions is quite screwy) which cannot be traced back to a direct chain of person-to-person transmission.  This criterion is easy to meet, and if you go back and look through the data (which the WHO has here), you can see that the conditions for a Level 6 pandemic were met at least one week before the declaration, and the WHO has admitted to waiting to make the announcement for political reasons (i.e. until the panic died down).   Indeed, speculation as to when the announcement would be made was bouncing around the media for quite some time beforehand (do a search for "swine flu level 6" and look at the dates on the articles). 

So what happens now?  Is H1N1 still a threat?  The answer to both questions is that we simply don't know.  Flu season is over in the Northern and Southern hemispheres (where most of the developed world is located), but flu season never ends in the tropical belt - which is inhabited by a much larger percentage of the world's population.  Unfortunately, this region of the world is also the one in which medical surveillance (and general medical care) is much weaker than the rest of the world - so for almost all practical purposes the virus is going to go silent for a few months before reemerging - and it will reemerge - when flu seasons begins again.  For a graphic showing how severe this surveillance problem is, check out the map below (source) - it's hard to believe that the belt stretching from Southeast Asia to South Africa has so few cases (pay special attention to the scale of the colors, they are somewhat misleading - 501 cases is the same as 5,001 cases).  When the virus reemerges, it could have combined with H5N1 or other flu strains, or it could have been weakened - we simply don't know and there's no real way to predict it.  I agree with the WHO's generally philosophy on the issue, which is to hope for the best but prepare for the worst. 

Bacteria are everywhere.  It's estimated that there are over 100 trillion (with a t) individual bacteria living in the average humans digestive tract.  While it sounds fairly disgusting (unless, of course, you're a microbiologist), their presence is actually a Good Thing - these bacteria help us to break down and digest foods that we would normally not be able to eat on our own.  However, sometimes this symbiosis has some unintended consequences, as this wonderful paper in PLoS ONE shows. 

Normally, our immune systems are used to the presence of our gut microbiota, but sometimes (fairly rarely) they provoke a spontaneous immune response.  Since it's not the body itself which causes the heightened immune response, it's not an autoimmune disorder, but the symptoms are very similar - in both cases, the body's immune system ends up attacking itself, which in the intestinal tract leads to Crohn's Disease and/or inflammatory bowel disease.  These conditions then increase the risk of colon cancer.  What this paper demonstrates is that modulation of the gut microbiota is enough to provoke this heightened immune response - and possibly lead to colon cancer.  Should you have time, it's a good read (it does get a bit technical though) but the real highlight (for me at least) is that it underscores the major role that bacteria play in just about everything.

With the ever-increasing use of medial imaging technology, such as CT scanning and MRI, it is now fairly common for tumors to be detected incidentally - that is, before they start to cause pain or produce symptoms on their own.  While this incidental detection is a Good Thing (certainly better then only discovering a tumor after it has metastasized), in the case of small renal masses (tumors <4cm) - which can be either renal cell carcinomas (kidney cancer) or benign - the best way to treat these tumors is still a matter of (very) heated discussion.  Standard procedure used to be a complete removal of the kidney - after all, we each have two, and if you remove the kidney you're guaranteed not to leave any positive margins.  However, some recent studies have shown that mortality increases after a kidney is removed - even from factors not related to normal renal function.  Consequently, there has been a trend towards removing part of the kidney in order to preserve renal function.  Surgical intervention is an inherently risky undertaking, and despite what medical TV shows would have you believe, the average patient is not  a young, attractive, generally healthy person - they are often elderly with many other comorbidities, such as heart disease.  In these patients, the surgery can often be more traumatic than the disease itself. 

The ideal treatment in these cases would be minimally invasive and tailored to the type, location, and size of tumor.  In other words, if the tumor is benign, it doesn't make too much sense to remove it - but you often can't tell if a tumor is malignant or benign from a CT image, so you have to remove it or take a biopsy.  If the tumor is malignant or high-grade (or even has the potential to become a nasty one) then it would be good to destroy it as effectively and as minimally invasively as possible. 

Focal therapy attempts to answer some of these questions and it approaches the problem from two angles:  the first is imaging (it's very hard to treat small tumors if you can't see them), and the second is therapeutic.  The field is still controversial (most of the work I will talk about here is pretty far outside the current mainstream - if you don't believe me look at what the AUA has to say about ablative therapy) and it's still very much in its infancy.  There are simply not enough data, but the research is quite exciting and the field holds huge promise.  Ideally, we would like to be able to image a tumor, determine how serious (i.e. what grade) the tumor is, and preserve as much renal function as possible while sparing the patient from unnecessary stress (i.e. invasive procedures). 

The ultimate in minimally invasive therapy is doing nothing - watching and waiting to see how the tumor progresses.  However, growth rates don't correlate with tumor grade, so you can't distinguish a fast-growing benign lesion from a slow-growing malignant one.  Next on the list are specifically targeted drugs - there is no surgery and they (in theory) only target the tumorous cells.  However, there are not any approved drugs (but there are many in development) which accomplish this goal.  After drugs, we move into surgical techniques - and the most accepted of these is a laparoscopic partial nephrectomy (removing part of the kidney).  However, since this procedure is invasive, if a patient has multiple comorbidities it can cause severe complications.  What's really needed is a step in between drugs and surgery - ablative therapy.  Ablative therapy uses extreme cold (cryoablation) or extreme heat generated by radio waves (radiofrequency ablation, or RFA) to kill tumor cells.  The effectiveness of these treatments remain unclear, but the idea is great - you can stick a needle through the skin into the kidney, check the placement of the needle with CT, and kill the tumor without ever cutting into the patient - and they can usually go home the next day!

My research over the summer (and what I presented on) focused solely on cryoablation - and the more we discover, the more questions we have to answer.  The optimal parameters for cryoablation are still unclear (How long do we have to freeze the tumor for?  How cold does it have to get?  How can we find out if the cells are actually dead?  Is using one needle or three needles a better treatment?  What does the 5-year survival look like compared to other therapies?), but it was great to see the massive research effort that is going towards answering these basic questions.  At the conference, I was constantly amazed by the caution, deliberation, and attention to detail surrounding every seemingly minor point - all to ensure that patients are treated in the best way possible.  I learned a lot from the conference, and am shocked by both how much we know and how much we still have to discover in this field.