Exposome Perspectives Blog

I forgot to remember to forget (Elvis Presley by way of Stan Kesler and Charlie Feathers)

Researchers place a high value on memory, and without memory how could we function, how could we learn, how could we even find our way home? We judge someone with a good memory to be fortunate and seldom consider any downsides to remembering.

Because the exposome of our past is what is shaping our health today, exposomics is about methods for reconstructing memory.

Exposome Perspectives Blog by Robert O. Wright, MD, MPH

Pity the poor poet!
I was always an avid forgetter:
in my two human hands
only the untouchable things of the world
live unscathed,
and the power of comparison required
nothing less than their total destruction.

From “Memory” by Pablo Neruda

Several of my blog posts have dealt with memory. Researchers place a high value on memory, and without memory how could we function, how could we learn, how could we even find our way home? We judge someone with a good memory to be fortunate and seldom consider any downsides to remembering. Environmental memory can be reconstructed with various tools—it may be embedded in a molecular assay like epigenomics that tells us about whether our mother smoked in pregnancy. It may be locked in an old photograph of our childhood we can analyze using artificial intelligence to estimate mood or socioeconomic status. We may gather data on our past from a questionnaire about our mother’s experiences during pregnancy.

Yes, memory is a powerful piece of the exposome, but today I want to focus on memory’s doppelganger: forgetting, an often forgotten (pun intended) corollary of memory. If we take a step back and think about how we go about our lives, it’s clear that the ability to forget is actually every bit as important as the ability to remember.  Without forgetting how could we get through the day? We would be bogged down with data overload. Our brains are constantly interacting with the world around us, planning, implementing and completing tasks. To complete any task requires an integration of continuums across two distributions: forgetting and remembering. By selectively remembering and forgetting, we reach decisions that drive our reactions to our environment. Each of us has trained our brains to sort out which memories to keep and which to discard. Without forgetting some of life’s details, decision making would be impossible, or at best incredibly tedious. We are so good at it that we take this skill for granted, and perhaps don’t even realize that forgetting is critical to our health.

So how does this matter for scientific endeavors? Is it possible that one of the biggest mistakes we are making in human research, particularly epidemiologic research, is not devising methods to measure, describe and quantify forgetting?

Long before scientists began to study the importance of forgetting, the great Argentinian writer Jorge Luis Borges proposed a life without forgetting. In a short story entitled “Funes the Memorious” he described a man who was incapable of forgetting any piece of information his brain received. Funes remembers every moment of his life in complete detail, but he cannot reflect on any single event or interaction because every perception he experiences is new, unique and constant—he can never pause, he can only catalogue. “Funes remembered not only every leaf of every tree in every patch of forest, but every time he had perceived or imagined that leaf”…..“it irritated him that the ‘dog’ of three-fourteen in the afternoon, seen in profile, should be indicated by the same noun as the dog of three-fifteen, seen frontally.” To him each memory of the dog was unique, not just the dog itself.  Because Funes remembered every single moment, every sight, smell, touch and sound he experienced in a day, if he were to be asked what he did yesterday, it would take him longer to recount the day than to live it.

Consider if you could get through a day if you were analyzing every detail of every experience. This is the biggest potential barrier to all the “omic” sciences—genomics, epigenomics, etc—sorting out what to remember and what to forget. There is so much to unpack in this story, analogies between Funes and “omic” sciences in general come to mind. The vast majority of what we measure in any omic science—be it genomics, epigenomics, transcriptomics, proteomics and even exposomics—has no meaning. We scan millions of genetic variants to potentially find a handful that are “possibly” important. We only ask “how do we sift through this mountain of information?” We rarely ask “why” do we try to measure so much information? Most of it is pointless to catalogue.  Perhaps, we should take a step back and try to sift out the unimportant information? 

Often when I write for the Exposome Perspectives blog, I try to link literature, art, and music to science. I sometimes think that comparing Borges and James Joyce’s Ulysses can be metaphors for the challenges of exposomics. I for one have learned more from Borges’s short stories than I did from reading James Joyce’s “Ulysses” — a 400,000-word reconstruction of a single day in Dublin. That single day for Leopold Bloom took me weeks to finish and often left me bewildered as characters and events were described without context. Too often I was unable to figure out what was important while trying to sort out the possible significance of mundane events—which were never presented again. Perhaps that was Joyce’s point—that our lives are filled with meaningless events and we have difficulty sorting them from what is important in life—but if so, it seemed to my younger self that I had spent too much time and effort on learning that lesson.  

Borges once described “Funes the Memorious” as a metaphor for insomnia. Funes himself, suffered from insomnia and can only sleep by imagining the trees across a distant field. He has never looked in that direction, because if he did, he would catalogue every detail of the forest and the intricate patterns of the branches. Once seen, they would cease to be an object of his imagination—his mind would be forced to catalogue each detail. Sometimes I worry that our approach to exposomics—the idea that we need to measure all our environmental exposures across time is akin to Funes the Memorious’s plight. We will be doomed to simply catalogue the enormous volume of information without taking the time to analyze it and separate the mundane from the important. We need methods to pare the exposome down into manageable pieces. In other words, we need to learn which parts of the exposome are better to forget. Nonetheless, I would like to make a pitch to quantify forgetting.

Of all human maladies, none are so tightly tied to memory and forgetting as Post-Traumatic Stress Disorder.  The role of forgetting is integral to the disease and may reflect a biological dysregulation. Forgetting past trauma can be a protective mechanism, but it is a complex relationship of voluntary and involuntary “forgetting”. Memory repression is unconsciously blocking thoughts or impulses, whereas suppression is voluntary and refers to deliberately trying to forget or not think about painful or unwanted thoughts.  We know that these types of forgetting occur following trauma, but perhaps forgetting is also inherent to our day to day formation of memory. We may be prone to forget certain types of information and that tendency may be a health indicator. One of the central tenets of epidemiology is information bias, i.e. when study data are either measured or recorded inaccurately. Recall bias is a form of information bias. It is defined as error arising when participants do not remember past events or experiences accurately or omit details. Recall bias is a particular problem in case-control studies that use self-reporting as cases (i.e. someone who has a disease) may remember past events differently than someone who is a healthy control in a study (i.e. how much did you smoke? How much red meat did you eat or how much tap water did you drink?).  Someone with a disease will think about their diet, health habits, neighborhood, home and childhood etc, much more with regards to how they may have gotten sick. They will remember more as they try harder.  Such incentives to “remember” are significantly lessened when you are a healthy control—so you may not remember.  But everyone, cases and controls, forgets some details, confabulates others, and does so at a baseline level they set in their developmental years. 

Most methods to address recall bias are designed to get to a more accurate estimate of exposure. But what about the size and direction of the so called “error”?  Is there useful information in understanding someone’s tendency to over or underestimate the past?  Might the degree of forgetting be representative of something harmful, e.g. early dementia or could it be a protective effect?  Maybe our ability to forget has value in a research context that we have not yet tried to determine. In a laboratory there are reasons why a machine may provide biased assay results—poor calibration, external conditions such as indoor air quality or humidity, or parts that are showing effects of aging and usage among others.  Perhaps we should take a greater interest in why someone forgets or misremembers the past when we administer a questionnaire?

Perhaps if we could quantify the basal amount of forgetting each person has, and whether forgetting arose from suppression (i.e. knowingly under or overestimating the past, i.e. like guessing your height or weight 5 years ago) or repression (not actually remembering, i.e. biologically losing the synapses that hold the memory) we could better understand the relationships between memory, cognition, behavior and health. At present we only try to estimate a single piece of this puzzle- the accurate memory piece.  There is likely important information in the inaccuracies as well, and forgetting can even be healthy. Perhaps John Prine sang it best:

“Today I walked down the street I used to wander
 Yeah, shook my hand and made myself a bet.
There was all these things that I don’t think I remember
Hey, how lucky can one man get.”

From “How Lucky” by John Prine