An intro to biology
With all this complexity, how do you begin to study the abundance of life around us? And then, how do we apply what we know about the zillions of organisms around us, to how they relate to what’s inside us?
The methodically classification and analysis of life is the science of biology, and like life itself it is a very broad field. Fortunately, despite the incredible variations, scientists have discovered a few simple traits and rules that apply to every life form. For the special life form homo sapiens, we have also learned a number of simplifications that will let us talk in more detail later.
A crash course in biology
A crash course in microbiology
A crash course in anatomy
The study of biology starts with the cell, those tiny self-contained blocks that you can think of as miniature chemical reactors that pull external molecules from their environment and reassemble them in ways that perpetuate the reaction. Everything in the universe tends over time to fall into disorganized entropy, but cells contain many tricks, honed over billions of years of evolution, to thrive.
Every living thing is composed of cells, but the types of cells can be broadly divided into two very different types: eukaryotes, which are the cells of everything from corn plants to humans to fungi and amoebas, and prokaryotes, which are always single-celled bacteria and other microbes. It’s interesting enough that all life could be characterized into these distinct groups, but if you look at the DNA that defines each cell, you will find some other odd differences that hint at more refined relationships among living things.
A cell’s DNA contains all the information needed to create another copy of itself; even the instructions for how to do the copying are just a sequence of predictable DNA letters written somewhere in the genetic code of all cells. This very important copying function is performed by a ribosome, which is a complicated but well-studied part of every living thing. Because the ribosome has such a fundamental function, it tends not to fall prey to many mutations over time; after all, a single DNA letter change in the ribosome is almost always fatal to the entire cell. But every so often — maybe every few million years — there is a mutation in some part of the ribosome, and this leads us to a clever way to understand better how living things are related to one another.
Humans and monkeys, for example, may differ in many different parts of their DNA, but their ribosomes are nearly identical. In fact, the ribosomes of all mammals and even all vertebrates are virtually the same. Well, there are some differences, but interestingly the differences between large, obvious groupings like vertebrates or invertebrates are much more significant than the differences between different vertebrates, or between mammals or other creatures.
In fact we can even quantify the differences, and scientists over the years have done exactly that. The ribosomes of humans and monkeys, for example, are different in only 10 places — practically nothing in a molecule that consists of a few thousand nucleotides connecting dozens of proteins. Similarly, the ribosomes of vertebrates and invertebrates are different in perhaps 100 places -- clearly much more significant than the differences within each grouping, but still not terribly different relative to the entire ribosome.
The ribosomes of prokaryotes and eukaryotes, on the other hand, can be quite different: perhaps 1000 places (to continue this very-rough-but-sort-of-useful metric). The point is that even at the molecular, ribosome level, we can see obvious genetic differences even if the physical differences between two organisms aren't necessarily obvious at first glance. A one-celled eurkaryote, like an amoeba or algae, for example, might seem like it should share something in common with a one-celled prokaryote, but looks are entirely deceiving: nobody looking just at the ribosome could possible mistake these as similar.
Now, scientists have mapped the differences in ribosomal structure among nearly all living things and this general rule always applies: the groupings of life forms are directly related to the similarities or differences in their ribosomes.
Meanwhile, scientists have made estimates of how long it takes, given various assumptions, for a series of step-by-step mutations to result in a differently-sized ribosome. In other words, using some basic chemistry that is easily demonstrated experimentally in a lab, we can offer some reasonable guesses for the number of generations it would take for a given level of random mutations to result in the differently-sized ribosomes we see in nature. Add it all up, and behold: you can see a reasonable fit with the clues we have in the fossil record and the geological record for the same creatures.
None of this is perfect, of course, but the point is that we have a crude way to quantify how different one organism is from another and, if you like, we can guess how long it would take for a single common ancestor to accumulate enough random mutations to account for the differences between any two life forms.
So far so good. Next let's imagine we have a circle, where a single cell begins in the middle, divides into two cells, and those cells divide, etc. for zillions of years until there are clear ribosomal differences between each line. Let's call this a family tree and take all known life forms and spread them into this circle.
If you do that, you'll find that the number of mutations necessary to generate all the variation found in eukaryotes -- everything from corn plants to people -- would take up only a tiny sliver of that circle. The rest of life --- in particular the microbial life of prokaryotes -- is so unimaginably diverse, that a space alien looking at earth's lifeforms could well conclude that the differences between humans and corn plants aren't significant enough to worry about.
That's how complicated the world of bacteria can be.
How do you talk about the relationships between various different life forms?
A taxon is a simple unit of life. A homo sapiens is a taxon, but so is a primate. A mammal is a taxon too. It might seem odd in the ordinary biological world to bother using the same term ‘taxon’ to refer to all of those units, but for bacteria and anything that reproduces asexually, it’s an important distinction because often, taxonomists don’t agree about whether a group of organisms is part of the same taxon or not.
Since Carl Linnaeus in the 1700’s, the science of taxonomy divides all life into seven major categories: Kingdom, Phylum, Class, Order, Family, Genus, Species (which I was taught in sixth grade to remember by the mnemonic “King Philip Came Over for Girl Scouts”).
Bacteria make up their own kingdom. Just as the animal kingdom includes everything from humans to jellyfish to beetles, the diversity of bacterial life is enormous, a point which can’t be emphasized too much. This is true at every rank in the taxonomy. Even two organisms that are the same at a lower rank, like genus, might have radically different affects on the human body, just as a member of the animal genus Canis could be anything from a wolf or coyote to a Chihuahua.
You cannot mix and match these ranks. If you know something about the number of organisms in one genus, for example, this is meaningful only in comparison to the numbers of another genus. Keep that in mind during our analysis.
All life runs on three chemical building blocks: DNA, RNA, and proteins. Each of these is an arbitrarily-long chain of repeating molecules called nucleotides (DNA or RNA) and amino acids (proteins). Due to constraints on the way atoms interact, the set of building blocks is fixed. All DNA is composed of only four nucleotides: adenine, thymine, guanine, and cytosine, represented by the letters ATGC. RNA is composed of the same molecules, except that uracile (U) is substituted for thymine.
Similarly, proteins are constructed with only 20 different amino acids, which can again be represented by a short three-character abbreviation.
The correspondence between these different proteins and combinations of DNA or RNA is referred to as the genetic code.
As a programmer looking through all of this, you may immediately be inspired to write your own software version of this. After all, the remarkable consistency between all of these building blocks cries out for manipulation by computer.
In fact, that’s exactly what bioinformaticians do, and numerous software packages have been developed to make it easy to treat these building blocks of life like ordinary computer strings.
Perhaps the biggest challenge is the volume of data to be handled, which can easily be measured in gigabytes for a simple organism, but can require entire server farms in the case of some real-world biological systems. For that reason, much of bioinformatics is about optimizations to improve the speed of processing a large data set, or to simply the presentation in a way that can reveal the most biologically interesting aspects of a problem without wading in over-complexity.
One special protein, DNA, can store information.
Finally, to round out our overview of how biologists study the microbiome, let’s get specific about aspects of our own human bodies, and break it down into components, each of which as we’ll see play hosts to unique microbial communities.
Somewhere near the border between the small intestine and the large intestine (colon), there is a small, pinkie-like appendage bulging inconspicuously into the abdominal cavity. For most of the period of modern western medicine, nobody knew its function, other as a source of severe pain when it occasionally exploded in infections that until the development of antibiotics were usually fatal.
Appendicitis used to be very rare (3-4 cases/year till 1890, up to 113 by 1918), which was fortunate, because there was no treatment. It was a sad fact that, for example the only death among the hundred or so frontiersmen and explorers on the Lewis and Clark expedition in the early 1800s was caused by appendicitis — a terrible, painful death in the wilderness but one that would have been just as inevitable at the finest hospitals in the world at the time.
What’s known is that the appendix apparently houses three things: tissue from the immune system, a bunch of what are called IgA antibodies that fight infections, and tons of bacteria. What’s also known is that people who have their appendix removed surgically — usually as a result of one of those terrible infections — recover to live apparently normal lives, with no side effects even decades upon decades later. So what is the appendix doing?
One clue comes from a recent study of 254 patients recovering from a C. Difficil infection, a horridly tenacious bacterium that has gained near-complete resistance to antibiotics and is notoriously difficult to treat. In the study, those with an appendix saw their infections come back 11% of the time, but those with no appendix suffered re-infection rates of 44% — a large and significant difference that has caused most scientists to speculate that the appendix is harboring something that enables the body to recover after a microbial disaster.
My own interest in this subject is not idle curiosity. About fifty years ago, doctors at a small town hospital gave an appendectomy to my five-year-old self in order to treat an unusual belly ache. While doing what was apparently an exploratory surgery to find the cause, they came upon my otherwise healthy-looking appendix and decided on the spot to simply remove it. “Why not?” I’m sure they thought at the time. “If nothing else, it’ll prevent him from appendicitis”, which is as tautologically sound a reason as any.
Did that change me, somehow? Am I fundamentally different because for most of my life I’ve been missing an important microbe safety zone that the rest of you enjoy? Science doesn’t know the answers, and even when there are studies based on well-conducted experiments, I can’t know the answer unless I do the experiment on me. [Hint: that’s exactly what I did: see Chapter 3]
Scientists have known since Pasteur times that our bodies and environment are awash in other species, microbial bystanders that seem to grow everywhere. But the techniques for uncovering which organisms are where and what they are doing was revolutionized in the first decade of the 2000s by those new-fangled gene sequencers that were so usefully applied to human genes.
The old technique for studying the microbial life around us required taking a sample, inserting it into a culture of some nutrient broth known to be good for breeding microbes, and waiting a few days to see what grows (or doesn’t). That’s still a common way to study microbes, and that couple-of-day incubation period is one reason you don’t get your lab tests back for a few days.
Now, thanks to new machines originally developed for mass DNA sequencing, the process of finding and understanding microbes has been revolutionized. It’s now possible to search for new life forms without growing them in a culture, and this has made possible a major shift in how to think about life —and what is important and special about human hardware.
Unlike the genetic discoveries you can make by understanding your DNA (from a low-cost consumer service like 23andme), much of the news from the microbial world is actionable. There’s little, if anything, you can do if you find you have a particular type of gene that gives you, say, a propensity to alzheimers for example. But because the microbes around you are constantly changing anyway, and because you can influence which ones grow and which don’t, the world of the human micro biome is eminently actionable.