Equilibrium

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I own some pretty good gross-out stories from childhood. It gives me great joy to reel them off at inappropriate moments and this is probably a strong indication of why I am rarely invited to formal dinners.

In the UK, fresh chickens used to be sold in the supermarket with a little plastic bag in the cavity of the bird, which contained the giblets and offal. When I was a very small girl, my father would prepare the chicken for roasting, and I would take the contents of the little bag, and sit on the back step, and happily chow down upon it. I don’t remember doing that, but, according to my mother, I loved slurping up the contents of that little bag. I do, however, remember very vividly summer days in our back yard, using little plant pots to collect interesting flowers and leaves from the few plants around the lawn. It was very satisfying for every pot to be at least half full of the same color buds or sprigs. I’d have a pot for nice, brown soil, and a pot for little twigs, and an ‘assorted’ pot. I was a big fan of compartmentalization. According to my little brain, these tubs contained ‘medicines’, and inevitably I would make tinctures of my medicines and carefully feed them to my younger siblings.

There is a pretty strong culture of germophobia in the west. Many people do, however, instinctively understand that, for a child, eating mud and bits of twig is no bad thing and fosters development of a robust immune system. This is how an immune system grows – it’s consistently challenged by little pokes, and the database of things to look out for improves, and solutions are coded for in case they’re needed in the future*. If you’re an adult – sure, go crazy: sit in the yard and eat dirt. Over the course of studying for my doctorate, I must have swallowed, cumulatively, at least a liter of raw sewage and I can’t really speak to the effect that had on my immune system other than the obvious disruption**. The key theme here, I think, is balance. 

Much of the microbiological study we scientists perform involves trying to pull a single bacterium, or groups of bacteria, from the environment so we can grow them in flasks of microbial chicken soup. If we're lucky, this produces a glorious broth, teeming with the bacteria we have lovingly isolated from soil, or water, or a gut, or the roots of a plant. Then, we can monitor their behaviors in response to prods and pokes - try to figure out why and how they do what they do.  Of course, removing a bacterium from its natural environment is like sending a human into space. They immediately start to behave differently. They become greedy and grow faster, they switch on different genes, they grow and die in unsatisfying regular and predictable iterations. The behavior of a domesticated microorganism no longer resembles its activities in the wild, where they are connected, directly, to the earth, and where they exist in equilibrium with their surroundings. The balance has gone.

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Pathology, or the development of a disease, often results (microbially speaking) from an imbalance or an over-proliferation. A good example of this is a type of colitis caused by Clostridium difficile. C. difficile, depending on which microbiologist you ask, is often referred to as a ‘pathobiont’: a potentially disease-causing organism which can also live as a symbiont with its host. Proliferation of C. difficile can lead to life-threatening diarrhea and inflammation of the colon. However, this organism is present in 1-3% of healthy human guts. Often the pathology is seen in response to high doses of antibiotics which wipe out bacterial populations who are otherwise keep populations of pathobionts in check.

Microbiologists don’t assign a moral compass to disease-causing microorganisms. There aren’t any ‘good’ or ‘bad’ bacteria – and if we were going to classify all microorganisms based on inherent capacity to do us humans harm or good, quite honestly there would be more nominations for downright heroic bacteria. Recent perspectives on the impact of the human microbiome on disease and well-being have led to spectacular claims that, some day, we may be able to manipulate microfauna to intervene in conditions such as depression, obesity, diabetes. A term used to describe microbial imbalances in a system, or impaired microbiota, ’dysbiosis’, has been leapt upon by industry folk who will provide all manner of supplements to cure it for you. Microbiologists aren’t sure if dysbiosis in a system is a feature or a flaw, or even a thing at all.

Antibiotics aren’t highly specific against particular groups of bacteria. That’s why, when treating infection, high doses can lead to the clostridiosis described above – you’re not just killing the bug you’re after. You’re killing vast numbers of everyone else present too. Inevitably, though, not every member of a community is susceptible to death by antibiotic (the Clostridia in particular are tough little suckers to kill) and those that survive have a clear advantage. The space is now cleared, there’s no queue at the buffet anymore. So now we have a situation in which an imbalance has led to pathology (an initial infection), and treatment (antibiotics) of that pathology has been (maybe) successful but produced a further, potentially more serious disease (clostridiosis).

Maybe we could figure out a way to kill only the potential problem children here, right? Perhaps, with targeted bacterial viruses who only kill one flavor of bacterium? It’s not a bad idea, and many of my colleagues are trying to do just that, with some promising results. But we don’t really know, ultimately, the nature of the impact this would have on an entire biological system – removing, completely, one member of a community who has been there all along, keeping to themselves, quietly and peacefully. This is currently a problem being faced head on by scientists working on gene drives. Gene drives re-wire Mendelian genetics and heredity – and in combination with contemporary gene-editing techniques, it seems like we could use them to completely wipe out certain groups of mosquitoes from the biosphere. We could prevent the deaths of more than 1 million people a year, mostly as a result of malaria, by killing all the mosquitoes that carry it. However, human scientists really have no clue of the eventual impact this is likely to have on the habitat the mosquitoes live in, or globally, even. Furthermore, consider: a virus and its bacterial host are engaged in a constant arms race of development of defenses and offenses, and they evolve very quickly. A targeted virus could, pretty easily, start targeting other groups of bacteria, and then what? Introduce engineered resistant bacteria to folks guts?

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There’s a little bit of hyperbole going on in that suggestion. But I have no answer to this idea of ‘imbalance’ in microbial systems, or what the best solution to treating disease is. At this moment in time, all the populations of populations of all the alive things aren’t in danger of being wiped out by disease. Just some of them. The system works, I guess? I guess, as long I’m not one of the ones in danger of being flattened – one of the ‘most-of-them’, and not one of the ‘some-of-them’. Hmm. Tricky. Mostly, we do what we can do, right? I often feel a great deal of imbalance in my life, day to day, and my slogan is the same: “I do what I can do, I do whatever works”. Often, at times of great upheaval and upset, when I feel like the universe is treating me unfairly, it’s very challenging to maintain perspective on this ideal. “I’ve been doing what I can do, and everything has still gone to shit, it’s not fair and I am being specifically singled out”. That’s ok. After the fact, and upon reflection, I can often see, however, how the turmoil fed back into eventual equilibrium. Big transitions require a field (life) getting churned up and debris (emotions, limbs) thrown out behind the back of a combine in order to change. In New Mexico, we have serious issues with wildfires, but wildfires can also be incredibly important to the ecosystem and development of forests. Stuff grows back. Or it doesn’t. Either way, there is change. Communities of microbes mediate change expertly, with great ease. They respond immediately and exactly to vagaries in the environment, and they make it work with aplomb. Or, they don’t, and they die with aplomb. But, the system as a whole goes on – not unchanging, but progressing.

So, where there is equilibrium, there is the potential for imbalance. In my own life, and I am sure in yours, too, the nature of that imbalance can feel unfair, painful, and even cruel. But to know suffering, you have to have also experienced blessings, and joy. To recognize a disease, you need to know what a healthy state looks like. So, what to do? Cling onto equilibrium in every place you can find it, all in hope of avoiding misery forevermore? I guess you could try***. But the pendulum swings, it brings me things, and by avoiding all suffering I also resign myself to never appreciating the opposite. One of my teachers once said to me “To fully commit to loving a place, to be willing to lay your life down in exchange for that place, you have to accept that one day you will lose that place”. A place, a person. Loss, death, disease. You get what you want, and the price for that is: you get what you need.

Bacteriophages at work. Phages are viruses who infect bacteria, and hijack their cellular chemistry to produce new baby phages. Often, the bacterial cell dies as a result. Phages are the most ubiquitous and genetically diverse entity known to humans. They play key roles, via the mediation of bacterial mortality and genetic transfer, in the global cycling of critical nutrients (nitrogen, carbon, phosphorus), microbial evolution and, among other things, the formation of clouds.

Bacteriophages at work. Phages are viruses who infect bacteria, and hijack their cellular chemistry to produce new baby phages. Often, the bacterial cell dies as a result. Phages are the most ubiquitous and genetically diverse entity known to humans. They play key roles, via the mediation of bacterial mortality and genetic transfer, in the global cycling of critical nutrients (nitrogen, carbon, phosphorus), microbial evolution and, among other things, the formation of clouds.

*In my professional capacity as a microbiologist, I do not advocate for feeding children raw chicken innards. That’s actually pretty weird.

**Again, I don’t advise this and I can assure you any ingestion of sewage was not voluntary.

***Spoiler: regardless of how hard you try, eventually you will fail anyway, presumed-human who is reading this.