Blog post #3

Science and Art: A Natural Connection

In lieu of a strictly science post, I wanted to talk about a passion of mine that is as important to science as it is to my person. It is something I fall back on during challenging moments in grad school. It is something I utilize when I am at my most confused, most stressed, and most happy. It is something I use to help myself, as well as other scientists and my fellow person. It is a critical facet to every field of science that is often overlooked in books, museums, posters, and classrooms. I am talking about my favorite scientific tool: visual ART.

When I define art as a “scientific tool”, I am not referring to a lab instrument like a scale or pipette. Nor am I referring to visual imagery for data analysis, such as graphs (although these do indeed communicate science to an audience!). Rather, I am referring to the role of visual art as a universal translator for the often complex nature of science.

The old adage “one picture is worth a thousand words” is extremely apt in this case. The ultimate goal of science is to better understand the world around us and communicate this understanding, but science is often perceived as “difficult” due to its multifaceted nature. Science can break down the simplest parts of life into insanely complicated individual components and overwhelm the reader with numbers and information. This complexity has built a stigma around the sciences that the public often references (we are all guilty of assuming the “scientist = smart” stereotype). The “other worldy” aura surrounding science, which is often perpetuated by unaware or high-flown scientists, has prevented many capable individuals from learning science for themselves. This can ultimately lead to abuse of knowledge or misinformation. Only by dispelling the stigma we have built around the sciences can we unite humans under a common objective knowledge that will improve the state of our lives and our planet.

Politics and personal opinion are the usual suspects to blame for scientific communication breakdown, but I argue that over-complexity is just as problematic. Think about it: how can you learn and apply new knowledge in, for instance, fisheries stock assessment if you don’t know anything about basic statistics or basic fishery principles? The experienced statistician may fully understand the definition of a regression, but he may not know anything about fish ecology. Likewise, the experienced fisherman with extensive fish knowledge may not know anything about the statistics underlying the fish population. What’s more, a person who is neither a statistician nor a fisherman may not trust, learn, or even care about new knowledge in such a field (and rightfully so, if they are not properly informed).The problem boils down to one question: How can you communicate a complicated topic to a wide audience?

Herein lies the rub. If I want to apply this conundrum to my current research, I face the challenge of communicating chemical concepts that may be very familiar to chemists, such as microscopic compounds in the environment and mass spectrometry techniques, but wildly foreign to everyone else. Posing the above question to myself: how can I communicate the complicated topic of chemical environmental contaminants to a wide audience?

Now, I am speaking from experience here. When I started this chemistry-based project, I was a marine biologist, pure and simple. My background was the macroscopic – small invertebrates, large fish, and the ecology of lake and ocean systems that supported these organisms. When I embarked on a project that characterized a chemical compound at least 5000x as small as the smallest creature I had studied, I found myself faced with a wall of seemingly insurmountable chemical knowledge. I had to spend months just reading about chromatography and mass spectrometry to scratch the surface of a topic that I could have learned much faster if given a straightforward learning aid.

This is where visual art fits into science. Visual art is a wonderful way of bringing science to a large audience since it presents intimidating information in a comfortable, simplified, and easy-to-digest format. Pictures have a way of simplifying complex topics into a cohesive image that our brains can assimilate. Of course, the image cannot convey all the details, but it provides a comfortable foundation for learning and a fantastic way of getting the “take home” message of convoluted data. Anyone can become intrigued by an interesting image since it captures the eye and engages the brain. In my experience, children are also much more likely to pay attention if given an exciting visual aid.

The principle of learning science through visual stimulation goes both ways for the artist and the viewer. Along with many students, I learn better if I draw an image of something I am learning. I have drawn illustrations for other scientists’ research projects that I know very little about, and ended up consuming a plethora of information about a niche field that I would not have learned otherwise. The act of moving my hands and engaging my brain to make a visual representation of the topic I am learning reaffirms what I know and enlightens me on what I do not know.

Personally, graphite and ink drawings are my medium of choice for learning and communicating complicated scientific topics. I have used my art to show specific biological structure, biochemical pathways, or biomechanical dimensions, and to convey general concepts in single images (e.g. neuroscience engineering, chemicals in the environment, etc.). I have even used art as a social tool in the lab to generate a sense of community between individuals (what can I say? People love to talk about a new picture!). Art is my go-to tool for working and learning effectively. Think of the potential for art to bring awareness to important complicated topics that would otherwise be misunderstood or brushed aside in the wake of confusion! Art has the ability to connect all of us as humans under a common framework of understanding.

So, next time you are at an art museum, or even just staring at the pictures on the walls of your favorite coffee shop, keep in mind that the same underlying skill that was used to paint, draw, sculpt, or craft aesthetic works is also the key to understanding art’s seemingly antithetic friend, science.

Hello Everybody,

It’s been a while since my first blog post, so it’s about time that I follow through with that second entry. As you guys may or may not recall, I am looking at the anti-diabetic pharmaceutical drug, metformin, as a contaminant of emerging concern (CEC) in the lower Columbia River. I know I promised to talk more about metformin as a drug, but I thought I would save this topic for next time. Instead, I am going to give a brief overview of my research methods that I have been busy developing for the past nine months.

In my last entry, I discussed the high incidence of Type II diabetes around the world and the discovery of metformin (the most commonly prescribed drug for Type II diabetes) as one of the most abundant pharmaceuticals being introduced into the environment. Metformin is not metabolized by the human body and excreted relatively unchanged into wastewater. Wastewater treatment does not necessarily target pharmaceuticals so much of the drug ends up in the environment.

My primary goal is to characterize metformin in the lower Columbia River in this environmental state. This means taking water samples and somehow measuring how much metformin is in each sample. So how do I do this? This is the question that I have been wrestling with since I started graduate school back in April. The short answer: Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS).

PLEASE DON’T RUN AWAY!! Those words scared me as much as you (unless, of course, you happen to be a chemist who loves chromatography). The LC-MS/MS machine scared me even more than that, until I understood that it is just an over-glorified “sorting machine”. I promise I’ll make this as simple as possible, for both you and me — it’s certainly what I’ve been trying to do since I first started my research. The pictures below sum up the bulk of my research and methods right now.

In fact, I’ve been participating in the OMSI Science Communication Fellowship to figure out how to simplify these convoluted methods. So far, I have completed three Saturday “Meet-A-Scientist” events where I try to communicate complicated scientific topics to a broad public audience (from kids to adults) by using a visual demo. I built a home-made “sorting machine” by reducing the LC-MS/MS machine to its simplest components. I would argue that I’ve learned more than my audience during this process – not only is my demo similar to the real machine in conceptual function, but it also requires an eerily similar degree of mechanical frustration.

(top) The Beast. Real LC-MS/MS requires a very scare machine. (bottom left) The Beast: Part Deux. Pretend LC-MS/MS also requires a very scary machine that breaks a lot. (right) The silver lining: kids love my home-made sorting machine!

What exactly is LC-MS/MS? Well, let’s start at the beginning: what is liquid chromatography (LC)? Liquid chromatography is just a way to separate something (i.e. a compound of interest) from a mixture. In my case, I use high performance liquid chromatography (HPLC) which is just faster liquid chromatography under high pressure.

In its most basic form, HPLC requires a column (“stationary phase”) and a solvent (“mobile phase”) — in other words, two things that will interact with your compound in different ways. The stationary phase column is a tube packed with tiny porous spheres. The mobile phase is a liquid that is pumped through the column with your mixture. The idea is that your mixture is pushed down the column with the mobile phase and each compound in the mixture will stick to the column for a different amount of time. The compounds with greater affinity for the stationary phase will be pushed off later than the compounds that have greater affinity for the mobile phase. The goal is to get your compound off the column without other compounds coming off at the same time. The column can be highly customizable to better separate your unique compound, such as sphere size, column length, and modifications to sphere surfaces. The mobile phase can also be customizable depending on your needs, although it is typically water, organic solvent (e.g. methanol), or a mixture of the two. As you can imagine, half the battle with HPLC is selecting the appropriate column and mobile phase — the selection process can take many months of expensive and time-consuming trial and error (this was the first three months of my project!).

HPLC is the first part of the LC-MS/MS machine. The machine injects the mixture (river water, in my case) onto the column and rinses the column with the mobile phase. My mobile phase is a solution of water and methanol that increases with time. As the methanol concentration increases, the compounds in the river water are “pulled” off the column at different times depending on their unique chemical characteristics.

(left) The HPLC column (stationary phase) is a tube packed with tiny porous spheres. (right) The idea behind liquid chromatography. The mixture plus a mobile phase solvent is injected onto the column and the compounds in the mixture separate at different times as they interact with the column and mobile phase differently.

The stuff coming off the column is recorded by the computer and represented in the form of a chromatogram, which shows the amount of material coming off the column over time. However, the question remains: how do we know which compound is coming off the column at which time? This is where the second part of the LC-MS/MS machine comes in.

The liquid chromatography tandem mass spectrometry (LC-MS/MS) machine consists of two parts: an HPLC machine to perform liquid chromatography (LC) and a mass spectrometer to perform tandem mass spectrometry (MS/MS). The computer represents the data with a chromatogram which shows the amount of material coming off the column with time.

Mass spectrometry (MS) is essentially just an extra step of “sorting” based on the specific mass of compounds. After your mixture has been separated by liquid chromatography, a mass spectrometer identifies the compounds coming off the column based on their unique masses.

The mass spectrometer first excites (i.e. ionizes) the separated compounds coming off the HPLC so that the machine can use charges to sort and pull the compounds through the machine to the detector. Specifically, the ionized compounds follow a path through an acceleration chamber and into a deflection field produced by two magnets. These magnets will deflect compounds differently based on their mass. Think of it like being shot through a cannon: the light cannonball will go farther than the heavy cannonball; Calista Flockhart will go farther than Mama Cass. The machine can be programmed to only let one specific mass, several masses, or all masses through to the detector. The detector will then record how much of each ionized compound is coming out of the mass spectrometer.

A basic mass spectrometer. The compounds coming out of the HPLC column are ionized and pulled through the system. A magnet deflects compounds differently depending on their mass. In this picture, the mass spectrometer has been programmed to detect all ionized compounds, but it can also be programmed to detect only one or a few masses. (picture courtesy of Khan Academy)

In my case, I use tandem mass spectrometry (MS/MS), which goes a step further and identifies the structure of the compound. A tandem mass spectrometer is just like a “basic” mass spectrometer, only the ionized compounds are broken into pieces in a modified acceleration chamber. Instead of sorting whole compounds based on mass, the machine sorts the fragments of compounds based on mass. You can then verify the structure of your compound of interest by looking at what fragments are present or not present. This is especially helpful if your compound of interest is in a mixture with other compounds that have similar masses, which is the case for metformin in river water.

Caption: A tandem mass spectrometer (MS/MS). The compounds coming out of the HPLC column are ionized and pulled through the system, just like in the basic mass spectrometer. However, MS/MS breaks up the compound(s) coming off the HPLC column into fragments. These fragments are then sorted by mass, rather than the whole compound. MS/MS can help verify the identity of a compound in a mixture of compounds that might have similar mass (as is the case for my river water samples).

THAT’S IT! LC-MS/MS is so simple, right?! Needless to say, the method development for LC-MS/MS is an extensive process. Nine months later, and I am just starting to realize this.

I am currently working with the OHSU Core Lab to fine-tune their LC-MS/MS machine for separation of metformin (and its primary breakdown product, guanylurea) from river water. I have a ton of Columbia River water samples from this fall that I am eager to run, so hopefully I will be able to start collecting data soon! In the meantime, I will try my best to separate any LC-MS/MS frustration from my mixture of scientific curiosity that brought me to this amazing graduate program!

Wish me luck!