Schroedinger’s Utility Belt, or How I Learned to Stop Worrying and Love Randomness

Biology has an amazing capacity to adapt in very specific ways. From learning (and generating) entirely new facts, languages and skills, to making antibodies to take down an infection, human biology is profoundly capable of generating specific biological changes in response to stimuli that are completely novel. On an intuitive level, it’s easy to equate this with the way human behavior often solves a problem—you observe a new stimulus, analyze it, and come up with response. And that’s where intuition fails to grasp how simultaneously haphazard and immensely clever biology can be. The reason your body can respond to just about any infectious threat it encounters is because every potential tool you need to mount an immune response against that threat already exists in the body, from birth. The front-line molecules responsible for detecting an infection and mounting a specific immune response—antibodies, and the T cell receptor—are assembled out of a myriad series of DNA fragments.  These fragments are separated into three categories, and a particular immune cell randomly grabs a fragment from each category to build its own particular receptor out of the 300 billion possible combinations, which will stick with that cell’s lineage as it divides over a person’s lifetime. So when an infection comes along, chances are that somewhere in that population of immune cells, one or more receptors and/or antibodies just happens to recognize some piece of the invading organism. Those cells start dividing like crazy, mounting a specific immune response against whatever’s giving you the sniffles. In short, your body doesn’t capture an invading virus or bacterium, analyze it, and come up with a countermeasure. Instead, the human body builds an enormous, random repertoire of countermeasures, and lets the particular invader select out which antibodies are going to be effective. Immunity is, if you’ll pardon the pun, a pre-existing condition.

The first time I learned this, which was in AP Biology, around my senior year of high school, it was staggering. How could the human body anticipate everything that the wide world of infectious organisms could throw at it? The answer, of course, is that it can’t, but that it manages to be prepared through sheer force of diversity. It doesn’t always work perfectly; sometimes an infection comes along and sets off a few antibodies that happen to also recognize normal, healthy human proteins, resulting in autoimmune disorders like lupus, or multiple sclerosis.

Novel experiences, while not as reliably dangerous as novel infections, pose just as much of a challenge for biology. How do you encode something unpredictable in a way that reliably stores information so that it can be used for your benefit when something similar comes around again? While neuroscientists haven’t fully cracked exactly how memories are stored in the brain, the leading contender involves—you guessed it—random selection.

The human brain has somewhere in the range of 100 billion neurons, and hundreds of trillions of synaptic connections. These synapses can be strengthened and weakened, formed, or pruned away, and it’s these changes at the synaptic level that are thought to store information, from memories, to skills, to life experience. These changes, referred to as synaptic plasticity, happen in response to different patterns of neural activity.

Among those trillions of synapses, there are connections just waiting to be assigned a meaning.  They carry some combination of sensory information, or represent one little complex piece of a muscle movement. When you experience something new—for example, learning about the ingenious randomness of the immune system—a burst of correlated activity hits your brain, causing a subset of synapses to release neurotransmitters. Other synapses might be sending signals around that time as well, telling you that you’re hungry or tired or that your nose itches, but they won’t be as correlated as the synapses that are responding to the new experience. When bound together by correlated neural activity, these connections get strengthened, others get pruned, and ensembles begin to form that, to the best of our knowledge, store memories and skills.

The plasticity that binds synapses together into correlated networks doesn’t create entirely new, unique pathways in the brain in response to each unique experience. Instead, the neural activity that accompanies a new experience largely selects among the pre-existing pathways, altering the synapses along those pathways. Though new experiences do sometimes induce the sprouting of new connections within a pathway, these new connections are often immediately subjected to selection based on neural activity as well. In other words, our experiences learning new things, practicing new skills, or even simply living our lives act as a selection agent for synapses, picking and choosing who fires when, and which groups of cells are active at the same time, assembling arrays of connections between neurons that map out the fabric of our lives, personalities, and skills. You often hear this expressed as Hebb’s law, the principle that, as my advisor Carla Shatz once coined: “neurons that fire together, wire together.”

What this means is that both the body’s immune and neurological response to the massive variety of threats and experiences that can come along in a human lifetime is a mind-boggling combination of preparation and probability. Like some sort of Schroedinger’s utility belt, an organism contains a whole range of possible responses, and then in the process of encountering a stimulus, selects among them. Despite our intuitive urge to identify, analyze, and design solutions to complex problems, it appears that biology sometimes prefers to take a strategy that’s half Charles Darwin, and half Boy Scouts: Be (Randomly) Prepared.