Toxicology in transit

A common theme in this blog is science communication: whether it’s advice on how to talk about your research at holiday get-togethers or how you can present your research findings to a scientific audience, I certainly enjoy writing about how to communicate, and I’m not the only blogger who does. But as the old saying goes, “those who can’t do, teach,” and perhaps I’ve been guilty of not following my own advice, even advice from my own blog posts.

At family get-togethers I tend to be the wallflower that greatly enjoys hearing about what my family is up to but the one who hates talking for more than a minute or two about what I’m up to apart from “Oh, you know, busy in the lab.” When meeting new people, scientists or not, I tend to give the same 5-second reply of “I’m a biologist” or “I do research” and move on to the next question or topic as quickly as possible. I feel guilty for this, realizing that I’m not doing as I preach in my blog, but in the moment of meeting someone or talking to my aunts and uncles about my work, I panic and resort to the easiest and shortest way out of the topic.

Lately, I’ve been thinking of how to become a better doer as well as a teacher in the realm of science communication. This has been spurred by being involved with outreach activities through my University, taking public engagement training courses, and, most recently, reading ‘Modern Poisons’ and seeing how my undergrad professor Dr. Kolok talks about toxicology. This week’s post is an attempt to layout my thoughts from the past few weeks on how to talk about my research in a way that will strike a chord with more people than just my fellow toxicologists, using an analogy that connects my research to another hobby of mine: public transportation systems.

There are a lot of joys you can experience while travelling: seeing new cultures, meeting new people, trying new foods, and feeling the vibe of a new city. For me, there’s yet another joy of travelling: maps. That excitement of getting a city guide that lists all of the key sightseeing points, but what’s even more exciting for me are the big underground railway and mass transit maps, displaying all the colorful connections throughout the city, the stops you can explore, and the numerous neighborhoods that are all within your reach.

The same excitement I get while looking over a new city’s mass transit map is the same type of excitement I got when first learning about molecular biology. I remember my fascination while sitting in the front row (yes, I was that person) of junior year molecular biology class at my alma mater, the University of Nebraska at Omaha, taught by the Biology department Chair and enthusiastic instructor Dr. Tapprich.  I was mesmerized by the intricacies of the biochemical pathways, how feedback loops between one enzyme to another in the same pathway kept every process related to metabolism under tight control, and how a system as complex as a human body could be interconnected through these pathways that are invisible to the naked eye. Perhaps my fascination between the two seemingly unrelated topics, mass transit and molecular biology, is due to their similarities. Public transportation connects a city of diverse neighborhoods and helps it function on a daily basis by moving people around, similar to how the intricately linked biochemical pathways control everything from our metabolism, immune system responses, organ function, and, in general, keep us functioning on a daily (and lifelong) basis.

But as we know in the real world of public transportation, a daily commute doesn’t always run smoothly. Somewhere along the line, a signal is down, a train gets backed up, or a train car has too many passengers getting on and off and ends up late to its next destination. A small snag can sometimes fix itself, maybe a late train makes up some time at the next stop, or a signal is fixed in a hurry. But when things don’t get fixed or when broken signals are combined with other malfunctions, the problems can grow even worse, causing delays that spill over and affect other lines, delays that seem to make the whole city come to a standstill. This is especially true in mega cities like London (see tube map below), a huge amalgam of interconnected lines, zones, and the inevitable delays on a regular basis, all while moving some 8.5 million people across the city.

Can you find your way around a town of over 8.5 million people? (Image from wikimedia commons, CC BY-SA 4.0)

​This is where toxicology comes into my transportation analogy: if molecular biology and biochemistry are the study of the lines and stops that interconnect a city, toxicology is the study of what a transit system can do when things go wrong and what happens when things can’t be fixed quickly enough to keep the city from devolving into disorder, chaos, and in extreme circumstances, complete shut-down.

But while you can study a map of the London underground on your own and fairly easily figure out how to get from Amersham to Oxford Circus, toxicologists learn more about the system by breaking it down into pieces, seeing how different train lines intersect, and seeing what happens in zone 6 when a train breaks down in zone 2. You’ll learn a lot in Dr. Kolok’s book about pesticides, which generally kill pests by over-stimulating an enzyme involved in transmitting neural signals. This would be like a broken signal at Ravenscourt Park which results in trains leaving the station every 30 seconds instead of every 5 minutes. At some point the trains will start colliding with one another, which is an transit-ified simplification of what happens in the neurological system after pesticide exposure: too many neural signal firings means muscles won’t be able relax, with a constant firing eventually resulting in a complete failure of the system.

For my PhD project, I worked with endocrine disrupting chemicals. The endocrine system is in charge of quite a few important functions in our body, but the most notorious are their control of sex hormones such as testosterone and estrogen. Chemicals that disrupt the endocrine system can create cross-overs and confusions in regards to hormone levels and normal development. Think about if you booked tickets to go to South Ealing but ended up arriving at Goldhawk Road instead. In my dissertation I studied a population of fish exposed to chemicals downstream from a paper mill. In this group of fish, the females had a growth on one of their fins that normally males only have-think of a situation where you happen upon a group of women living in a remote area who all have thick moustaches and beards.

Using the publication transportation as a model for toxicology, you can start to imagine the connections between different body systems as well as how things can go wrong at any point along the map. Toxicologists need to understand what happens at the stations, the rail lines, and all the interconnections between places and routes in order to address questions like why a signal failure in Kings Cross can delay trains in West Brompton. In general, toxicologists study very specific trends: what happens when this enzyme doesn’t work or works too well, why a synthetic chemical can cause endocrine disruption, etc. It’s also a way that we classify toxic chemicals based on what lines they impact the most, what stations they hit, or how easy they are to clean up afterwards.

But what if the problem wasn’t at a specific line or station? How would you study the system if instead of something specific like a signal failure, there was an earthquake? In theory, just about any part of the system could be damaged, ranging from a minor delay due to a small magnitude quake or catastrophic destruction in the event of a large magnitude event. But as countries who live in earthquake-ridden locations know best, there are generally particular areas that get hit the most that can be reinforced to withstand a full-blown earthquake, weak points in a city’s infrastructure that tend to feel the brunt of even a small earthquake more so than others. But how do you find out what these weak points are without waiting to see what a big, potentially damaging earthquake can do firsthand?

The earthquake within this ‘toxicology in transit’ model is called narcosis, and it’s what I’ve been studying for the past 2 and a half years of my post-doc. Narcosis as a field of toxicology has been around for a while, but exactly how narcosis works (i.e. what stations and lines get hit the worst during an earthquake) is still uncertain. We know that narcotic compounds target biological membranes, the master gatekeepers and regulators of what goes in and out of a cell. Cell membranes are like the ticket gates at the station entrance: you can only get in (or out) if you have the right ticket. Membranes have to be good at controlling what is allowed in and out to make sure your cells have the right balance of ions and proteins so the cell can keep running normally. Narcotics break down this barrier and change the properties of the cell membrane, effectively letting anyone in (and out) instead of keeping things tightly regulated.

But the problem is that we don’t know exactly what happens when membranes go wild. Think back to the transit example with an earthquake: Do all the train signals stop working, or just a select or key few? Are there delays on all the lines, or are there a few key lines that once they get out of whack cause the whole city to be in disarray? While my project is still ongoing, it looks like it’s the latter that can explain what we see in narcosis. Narcotic chemicals tend to impact neurological signaling, and in my project we’ve found that biochemical pathways related to neuronal function tend to be more impacted than others. While the narcosis earthquake is still a random event in that any membrane in a cell can be impacted, the ones related to sensation and body movement tend to get hit more than others. This allows us to take a closer look at the stations and rail lines impacted by an earthquake, and to better understand more precisely how narcosis happens and why.

 So that’s my post-doc career in a nutshell: studying cellular earthquakes and transitioning my love of travel maps into a career in science. While I came up with the idea on a bit of a whim, I’ve found that getting started with actually putting thoughts into words and concrete ideas is the hardest step, and perhaps also the scariest: you feel like you’ll get something wrong, or that you won’t be able to write something as clear as you see it in your head, or that you’ll go through all the trouble and still have no one who understands it. My only advice here from the ‘teacher’ side is to just give it a try. If something doesn’t come out perfectly, you can always try again and learn from what did and didn’t work the first time around.

During the rest of the summer I’ll continue putting my science communication skills into the ‘doing’ stage and will also have some additional posts on science communication approaches and techniques. Next week we’ll revisit our Heroes of Science series, and we also look forward to some upcoming collaborations with the Ecotox blog and the EuroScientists blog. Until next week, we wish you a summer of delay-free commutes (if there is such a thing!).