Yosif (Joe) Zaki

Neuronal hills and valleys

Project 1 Final Draft
ENGW3307
Date: February 5, 2018
Documentation Style: AMA
Word Count: 2227

I started taking photos when I was 15. When I picked up a professional camera for the
first time, I was allured by the dozens of buttons and switches that adorned it, each with its own
discrete function. I thought, how could photography—a practice often described as “creative”
and “artistic”—be so calculated and technical? I had always had a stronger affinity for the
sciences than I had for the arts, perhaps because I was drawn to the technical discipline I
understood science to be. But there I stood, holding a contraption that straddled the two worlds—
two worlds that, up until that point, I thought were non-overlapping.
I have been taking photos ever since. Discerning the functionality of my camera was my
initial intrigue, but learning to create a story from my worldview was what kept my attention for
the next eight years. I found early on that it wasn’t difficult to hold up my camera and snap a
bunch of pictures using arbitrary exposure settings. What would likely result was a decent
picture, but it would often miss the nuances that the eye could capture much more readily. Take
the following three pictures of the same scene from my trip to Georgia last summer, for example.
They each try to capture one striking element of a particularly dynamic scene. The first tries to
capture the grandeur of the sky, the second focuses on the laziness of the river, and the third
attempts to parse out the intricacy of the hilly landscape. But each picture neglects the other two
elements of the picture, simply because a camera can only take a picture at one exposure at a
time. But an eye, of course, can look onto a bright sky and a dimly lit river concurrently. With
any one exposure, it would be impossible to paint this scene with a camera the way an eye could.

But now take the following image, which is a merged version of the above three images.
It is a lot more representative of the scene I was looking onto, and it’s because it properly
exposes all the details of the scene. After all, isn’t that the purpose of photography—to solidify
an experience in a way that captures all the notable details of the memory? And isn’t it strange
that such an artistic product had to undergo complex computational algorithms to blend multiple
exposures into one? I certainly thought so, and this seemingly paradoxical idea that calculated
procedures conferred artistic creations had me—and continues to have me—mesmerized.
 I came to college to study neuroscience—a seemingly purely technical field. When I
conjured up an image of a scientist, I would picture someone who followed rigid protocols and
had clear views of the future of science. I understood no more than that about what a scientist
was, and thus, I would never have used the word “creative” to describe science.
Early on in my undergraduate career, I was taught about Santiago Ramón y Cajal, a
neuroanatomist who won the Nobel Prize for his work on elucidating the structure of the nervous
system. It turns out that when he was young, he was deeply interested in art, but he chose to go
to medical school where his father was a lecturer. There, he drew the structures that he observed
under a microscope in meticulous detail, and these drawings became the first evidences of
today’s canonical view of nervous system structure—that is, that neurons are discrete units that
are interconnected through tiny spaces between them that we now call synaptic clefts1. But what
stood out to me was that he expressed his scientific findings through drawings! Based on the
separation between science and art that I had painted in my mind, this approach didn’t make
sense to me; drawing was for artists and discoveries were for scientists. But this guy seemed like
an artist to me more than he did a scientist: he was drawing the world as he observed it.
When I joined my first laboratory during my second year of college, the precise and
calculated nature that I had always envisioned of science quickly manifested itself around me.
People were running around wearing lab coats and driven faces, reading printed protocols, and
following strict schedules. I would have never confused science for an art form. And one day, I
noticed a book in the lab titled, “Advice for a Young Investigator,” and a coworker suggested that
I read it2. I was, in fact, the youngest investigator in the lab.
I went home and carefully deciphered the lessons that the author claimed would lead to a
successful career in science. There were discussions on being independent as a thinker and
excerpts on being suspicious of already published science. The book read almost like a protocol,
and described very objectively how a successful career in science could be attained. A scientist
must have written this book, right? But when I flipped to the front of the book, I saw “Santiago
Ramón y Cajal” written in big letters on the cover. The same person who I thought of as an artist
was also this calculated and technically-driven character. Maybe the worlds of science and art
interacted more than I had originally imagined.
A few months into working in that lab, I was tasked with learning how to use a
fluorescent microscope, which was a big piece of equipment that we used to visualize samples of
brain tissue. Sitting down at the microscope for the first time felt a lot like the first time I held a
professional camera; I found myself fidgeting with buttons and switches all over again, and after
months of fidgeting to unveil the functions of the microscope’s parts, it occurred to me how
similar my learning experiences in photography and microscopy had been. Both began with the
simple goal of understanding a new piece of equipment, and ended with a much more formidable
goal: to observe the world in a different way than my eye normally could, and to accurately
depict those observations. Even the microscope images that I was creating were reminiscent of
the landscapes that I was capturing. The following microscope image is of neurons in a rodent
brain that I took this past year, and the hills and valleys of cell layers in it remind me of the
seemingly never-ending horizons I witnessed in Georgia last year.
After observing many cellular structures under the microscope over those initial months
and for years since, I no longer think of science and art as two disparate schools of thought. In
fact, I now ascribe a lot of my creative thinking to my scientific endeavors.

From observing the world through my camera lens, I forayed into exploring the world
through a scientific lens. In the lab, I was introduced to reading scientific literature and thinking
“critically” about science, a concept that teachers often alluded to, but one that I had never
formally been introduced to.
When I began reading scientific literature, I was severely overwhelmed by the jargon.
And on top of the jargon, papers demanded that the reader understood the methods thoroughly,
could decipher the purpose of the experiments and their results, and most importantly, could
tease out how the results fit into the scientific narrative that scientists were trying to construct
around that phenomenon.
The approach I adopted to learn to read papers was to assume truth in everything I read.
After all, I was so accustomed to memorizing ideas straight out of textbooks from years of
schooling. I was unfamiliar with being critical of scientific writing; I had never been taught how
to be. But one formative experience allowed me to look at science in a very different way:
In several courses, I was taught that when a long-term memory is stored, there are
changes in protein synthesis in the brain that reflect this learning; in other words, long-term
memory is dependent on protein synthesis. That makes sense: there must be changes in the brain
that accommodate learning episodes, and it turns out one of those changes is protein synthesis.
This was an idea that was made famous by Eric Kandel, a neuroscientist who studied learning
and memory in sea slugs. His primary experimental design involved touching the siphon, a part
of the slug’s body, and observing the slug’s gill withdraw into its body as a defensive response.
And his group found that long-term responses in the gill withdrawal reflex were protein synthesis
dependent. In fact, this idea was so ground-breaking at the time that Kandel won the Nobel Prize
in 2000 for it3. And since then, this concept has been reaffirmed in many ways. For example, if a
protein synthesis inhibitor is injected into the brain during a learning task, long-term memory is
impaired4.
In 2015, however, my supervisor in the lab I was working in recommended a paper to me
that challenged this notion that protein synthesis is necessary for long-term memory. To leave
out the jargon from the paper, here’s the meat of it: the group blocked protein synthesis with a
protein synthesis inhibitor while a mouse learned a task, but at the same time, they labeled the
cells that were thought to store the memory (which happened to be the cells that were active
during learning). Days later, when they placed the mouse back into the environment, it showed a
deficit in recalling the experience, as was expected based on Kandel’s previous work. But when
they activated the labeled cells (thereby “activating the memory”), they found that this allowed
the mouse to express the learned behavior5. This indicated that protein synthesis may have been
important for the expression of the memory, but not necessarily for storing the memory in the
first place. But I was confused; didn’t Kandel show through his work that long-term memory was
dependent on protein synthesis? It turned out that while Kandel’s findings weren’t incorrect, it
seemed that this phenomenon was more nuanced than was originally thought and generally
accepted; while protein synthesis changes had been observed during learning, they did not seem
to be necessary for storing the memory, since the memory could be forcibly expressed without it.
Reading this paper irked me. I had been taught so many times about Kandel’s
experiments in class, and eventually, the minutiae of the experiments had boiled away to leave:

long-term memory = protein synthesis

in my head. But that’s not what those experiments demonstrated; they only demonstrated that
protein synthesis accompanies learning episodes and long-term memory storage. No further
dynamics of this phenomenon had been explored through that work, but I had unrightfully
generalized the findings to simplify my conclusions. But science is more nuanced than that. The
brain is more nuanced than that.
The teaching that I had experienced in the classroom had created an illusion that most
things are largely understood. In the laboratory, I quickly learned that many phenomena are not
well understood, and this reality alone provides scientists with careers to explore them. In class, I
had been recited the findings and conclusions of past science, with little emphasis on the holes in
science that had yet to be filled. In the lab, we used past science to shape the experiments that
would ultimately fill those holes. And very fortuitously, the shift I experienced in focusing on the
“understood” to the “not-yet-understood” coincided with a shift in the teaching paradigms I was
experiencing in class:
As I completed my lower level courses at Northeastern, I began to take higher level
neuroscience courses that covered more specific topics—developmental neurobiology and neuro-
immunology, for example. While those curricula conveyed the “understood” about their
respective topic, they added a tasteful element to the course that introduced us to the “not-yet-
understood:” journal club. Journal club involved reading one paper every week that accompanied
the part of the lecture we were covering. If we were covering segmentation of the nervous
system in class, we would read a paper on segmentation of the nervous system. But how did
reading a paper of past science help in any way to highlight the “not-yet-understood?” The
answer is that the papers we read in class were current, like written-in-the-last-five-years current.
An idea could have still been explored in 2014, while the textbook that covers it was written
years before that. Through journal club, I much more readily noticed the holes in science from I
learned in the classroom, because some of those holes would be addressed in the papers we read.
So, it turns out science is merely an iterative narrative with nature as its protagonist, and a
little bit more is learned about our protagonist every time they are revisited. But a photograph is
a narrative, too, perhaps also with nature as its protagonist. So, science is merely a well-
disguised art. It took me my undergraduate career to recognize that.
I oftentimes get caught up in a story and need to know what happens to the protagonist in
the end. Nature’s is a slightly different story, because I’ll be gone before I know how the story
ends. But I have found that I like writing stories as much as I like hearing them, and conducting
research is a way of unfolding nature’s story. There will always be more to unfold; as Ramón y
Cajal describes, “the infinite is always before us6.”
Acknowledgements
I would like to thank Drs. Patrick Davis, Steve Ramirez, and Giuliano Iurilli, for being
invaluable mentors for me throughout my undergraduate career. I thank Drs. Steve Ramirez,
Leon Reijmers, and Bob Datta, for providing me the resources to flourish in their respective
laboratories as a budding neuroscientist. I would also like to thank Dr. Cecelia Musselman,
Rachel Dewar, and Kerste Milik, for allowing me to distinguish between what I wanted to
convey in this piece and what I was actually saying. I thank Jake Campolo for keeping me
interested in science outside of neuroscience, and for being a major relay station for my ideas.
And lastly, I thank Katie Kerr for never letting me forget the inextricable link between art and
science.

Works Cited

1. Santiago Ramón y Cajal – Biographical. Nobelprize.org.

https://www.nobelprize.org/nobel_prizes/medicine/laureates/1906/cajal-bio.html.
Published 2014. Accessed February 5, 2018.
2. Cajal SRCC. Advice for a young investigator. Cambridge, MA: MIT; 2004.
3. The Nobel Prize in Physiology or Medicine 2000. Nobelprize.org.
https://www.nobelprize.org/nobel_prizes/medicine/laureates/2000/. Published 2014.
Accessed February 5, 2018.
4. Meiri N, Rosenblum K. Lateral ventricle injection of the protein synthesis inhibitory
anisomycin impairs long-term memory in a spatial memory task. Brain Research.
1998;789(1):48-55. doi:10.1016/s0006-8993(97)01528-x.
5. Ryan TJ, Roy DS, Pignatelli M, Arons A, Tonegawa S. Engram cells retain memory
under retrograde amnesia. Science. 2015;348(6238):1007-1013.
doi:10.1126/science/aaa5542.
6. Anderson ML. Santiago Ramón y Cajal’s Advice for a Young Investigator. Dana
Foundation.
http://www.dana.org/Cerebrum/2016/Santiago_Ram%C3%B3n_y_Cajal%E2%80%99s_
Advice_for_a_Young_Investigator/. Published October 13, 2016. Accessed February 5,
2018.