Electron microscopy images of bacteriophage docking on and injecting genetic material into a bacterial host.

Electron microscopy images of bacteriophage docking on and injecting genetic material into a bacterial host.

The Infinitely Big in the Infinitely Small

Saturday, December 3, 2022

Third place winner in the Synapse Storytelling Contest nonfiction category.

The typical existential thoughts of a graduate student drifted through my brain in my first year of school: What do I want to do with my career? Am I in the right place? Is this all worth it?

Should I just take drop-out, enroll in a coding bootcamp and become a van-lifer? What I wasn’t expecting was the ones that nestled in my mind this past spring: Who am I? What am I? And, the kicker: What is the meaning of life?

It all started in my final lab rotation. I was rotating with the Bondy-Denomy lab, which studies the evolutionary arms race between bacteria and the viruses that infect them, bacteriophage (known as phage for short). I was live-imaging a special type of phage on a fluorescent microscope. I monitored its quick “life”-cycle: infection of a bacterial host, replication within and lysis to release phage progeny. It was fascinating; the blue fluorescing dots (the phages) docking on small rods (bacterial cells), the blue entering the rods and growing massively and quickly in size until, eventually, the rod burst open like an erupting blue paint ball. 

It was thrilling to watch, but it also made me feel a bit uncomfortable. It was so violent, and it happened so fast. And once the progeny phages were released, they would just move on and repeat the process again on another bacterial victim. In the dark of the microscope room one day, I asked out loud “what’s the point?”

Phage are really cool, but also kind of creepy. High resolution microscopy images of phage docking on bacterial hosts look like a giant spider latching onto someone’s skin, or a rover landing on a previously unexplored planet. The sheaths that house their nucleic acid are probe-like, and injection is blatantly non-consensual. Fluorescence microscopy images of 1mL of sea water housing millions of phages looks like images of faraway galaxies captured by a deep-space telescope. 

In structure and function they are strange, but in terms of identity, one could argue they are even weirder. They mutate at incredibly high rates, leading to rapid molecular evolution, and easily recombine their genomes with each other to share advantageous genes. Given their rapid reproductive time frame, one can imagine how quickly a phage can stray from its “original” genome. Indeed, virologists don’t even like to ascribe one genome to a particular type of phage. Phage and other viruses are instead referred to as a quasispecies, a distribution or “cloud” of related genotypes and mutants. This makes the concept of an individual viral particle puzzling to think about; where does one draw the line between individual and population?

Perhaps what makes phage the most disconcerting, and what heightens the eeriness of all the aforementioned details, is their… simplicity. Most scientists today would not classify a phage as living. It’s a parasitic bag of molecules. But that bag of molecules actually has a lot of things in common with living things, at least fundamentally speaking. It grows, changes, reproduces and eventually dies, albeit at the mercy of another entity. It’s subject to evolutionary pressures. And it follows the central dogma of molecular biology drilled into our cells (and brains): DNA to RNA to protein (although admittedly, some viruses are crafty and skip the DNA part). It does a lot of the things we do, just a radically faster time scale. And it does this all with arguably the minimum amount of genetic instructions. 

I kept thinking about the phage’s “identity” and “purpose.” Perhaps this was a fruitless intellectual endeavor, because what is self-actualization and the meaning of life for something that isn’t sentient or living? But perhaps this minimal genetic code, this simplest collection of changing biological components, has something to teach the living. Especially considering the fact that the majority of us living things are literally brimming with bacteriophage and other viruses. Though the numbers are still up for debate, it’s estimated humans contain 10x more virions than their own cells. Not to mention that 8% of our genome is viral (while only 1% is actually used to make protein products). We’re each an exciting planet for viruses to “exist” upon. 

So if a virus can be thought of as a minimum entity of the fundamental components and rules of life, does that mean the meaning of life is just to… reproduce? …Until you can’t anymore? Perhaps yes. And if more of our bodies and genomes are viral than human, are we just a surface for microorganisms to wage their own reproductive and evolutionary battles? Probably also yes. For me, these were disturbing thoughts at first, but when I realized their consequences, it actually brought me comfort. Our biological molecules will “live” on, in our own progeny (if we choose to have them), or in the endless multitudes of microbes that spend their lives upon us. What is death but a pure recycling of building blocks from one bag of molecules to the next? Jean Paul Sartre, infamous existentialist, once said: “Life has no meaning the moment you lose the illusion of being eternal. Life has no meaning a priori… it is up to you to give it a meaning.” Unfortunately, our sentience is decidely not eternal. But molecules on the other hand; those are forever. And for me, that’s good enough.