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they evoke thoughts of classic pharmacology. drug binds to receptor, forms drug-receptor complex, evokes downstream actions, dissociates. one visual representation of drug binding at various concentrations is a very nice looking S-shaped curve known as a dose-response curve. these are among the very first things you learn as a training pharmacologist. (then, if you’re in my program, you get hammered with pharmacokinetics math by the very best. and you hate life for a month but you get it.)
i have done hundreds upon hundreds of these assays on various samples for different projects over the past few years, and can do the things in my sleep with one hand behind my back. really, they’re very simple until something goes wrong- but require some pretty intense concentration if you’re going without automation. in fact, this past week i got another set of 100 related assays started at maximum daily output. to double my output, i’m working to bring back my most stellar undergraduate student for a few weeks.
even diagnosis isn’t too painful. you gauge your results and narrow down the possibilities. you make a change, run the assay again, evaluate the results. it’s good for sucking up a lot of time, though- time most of us don’t like to spend in diagnosis mode.
despite being a fundamental pharmacological assay, and despite the solid data one gets from them, i find the incredible monotony mentally draining. there’s nothing like pipetting things into assay tubes all day to get the brain to atrophy. if the most exciting part of my scientific day is seeing an r-squared value of 0.98 while cracking open my 4th 12oz caffeinated beverage for the day, i’d say my life is pretty pathetic.
not that 0.98 isn’t too damned shabby for real tissue and the occasional lapse in focus while pipetting 16 different drug concentrations into 300some different tubes. and this stuff is better than other things i’ve done in labs. but i just came off an extended run with immunofluorescence, and cool glowing brains are a tough act to follow.
the harder i work, the sooner it’s over. with the high-energy, high-intensity way i do things, i’m exhausted at the end of the day. but thanks to a really good group of coworkers, the time passes fairly enjoyably in the big picture.
this is something i’ve been working on here and there, as i had some free time or couldn’t sleep or whatever. i hope that someone, somewhere finds it helpful, because a basic layout of the disease is kind of hard to find for the average person who can’t read research literature and is seeking a plain-language discussion. the highbrow medical language of the literature was enough even to intimidate me as a basic scientist.
Susac’s syndrome is a rare disease that has been identified in about 200 patients worldwide. It is characterized by a triad of symptoms: loss of visual acuity, loss of hearing, and encephalopathy which can be mistaken for acute disseminated encephalomyelitis (ADEM). While its causes remain unknown, several factors seem to be at play as things go haywire. There appear to be autoimmune, vascular (blood vessels) and inflammatory processes involved.
All we know about Susac’s comes from clinical experience. This isn’t all that surprising, given how few people actually have the disease. We do not have experimental models to tinker with, and real people don’t want to waste any time when it comes to treating the symptoms. Basic science hasn’t even had a crack at this mystery, and probably will not for years to come. It’s unfortunate, since a proper model of the disease would give us a great deal of insight into causes, treatments, outcomes, etc. We could learn much, but until we reach that point the focus is on getting patients back to their normal lives.
But not all patients show the same symptoms, or show all of them right away! This is part of what makes it so hard for doctors to diagnose this problem, and why it is often mistaken for other diseases. It is also a likely reason that so few people have been diagnosed with Susac’s- it can be very hard to pinpoint. There could be a lot of people out there who have Susac’s but have not been properly diagnosed because of insufficient evidence.
Encephalopathy literally means a disease of the brain. So let’s look a little more specifically to what goes on in the brain in Susac’s syndrome. The corpus callosum is in the middle of your brain- it connects the two hemispheres and allows both sides to communicate. One of the things that you will see in Susac’s is that the corpus callosum has lesions, it has pinpoint holes. These are caused by blockages of small blood vessels in the brain. These blockages seem to be the result of a local autoimmune reaction against the interior of the blood vessel wall. Unfortunately, our immune systems are tenacious (even against our own bodies in the case of autoimmune disorders), so this is a devastating attack. Since these lesions are basically impeding communication between the halves of the brain, and they can occur in various locations, the results are variable. To make it more complex, lesions can occur in other specific parts of the brain. Movement, memory, personality, and speech problems are all things that can occur as a result of these lesions. Of course, this does not cover ALL of the possibilities, just a handful of them.
Arterial occlusions of the retina, or blockage of the blood vessels in the eye, are the cause of visual problems in Susac’s syndrome. In some cases it appears there are plaques on the blood vessel walls, in some cases this is not seen. What brings these plaques about is unknown, but does not seem to be related to a clotting disorder. The reaction is likely to be similar to what is occurring in the brain. The severity of this hearing loss can range from a small spot to the entire eye, depending on the location of the occlusion.
Microinfarctions of the cochlea, or blockages of small blood vessels in the ear- is this sounding familiar yet?- can cause hearing loss through the same process as the damage to the corpus callosum and the retina.
As far as treatment, the recommended course is fairly typical for autoimmune disease. The intent is to stop the immune reaction and inflammation. Corticosteroids are used to decrease inflammation and slow the immune response. Other lines of treatment include immunoglobulin, which is a solution of purified human antibodies. While we have not confirmed how, treatment with antibodies appears to attenuate the immune response in patients with autoimmune disorders. Other drugs, such as the cell proliferation inhibtor cyclophosphamide, may also be used. Cyclophosphamide keeps the population of antibody-producing cells (and therefore the anti-self antibody) low by causing DNA damage. It doesn’t affect all cells because of its mechanism of action, but does tend to affect certain populations of rapidly-dividing cells. In one case, hyperbaric treatment helped to reverse the vision loss.
Outcomes vary, as expected with a very small sample of patients to study. Some patients regain full function within about 5 years. Some continue to deal with residual effects of the disease, and some deal with permanent disability. Early intervention seems to be important, but we have little data available to predict outcomes. We can only hope that as time goes on, our ability to diagnose and treat this illness will improve and we will gain a better understanding through experience and study.
and on a personal note:
i love you, sis. keep up the hard work and you will reach those goals despite the troubles you’re going through. remember, as long as you set your mind to it, you’re stubborn enough to do it. just like me. i am always a phone call away if you need me. i’m working hard to get closer to home next year.
thank goodness for overnight shipping. i’m pacing the floors here.
i thought i had everything up and running and dove into my first tissue samples, only to find i wasn’t so happy with the numbers i got. something is not quite right, with a right shift in the binding curve and the bmax being way lower than i’m used to seeing. i made a point of using vehicle treated tissue first, to be sure.
man, and there’s really nothing more beautiful than a nice sigmoidal curve. the r-squared value was awesome, but it’s not what i should be seeing.
new chemicals arrive tomorrow. i also just stocked up on caffeinated beverages, i’m gonna need em.
the upside is that i had the time to attend a talk from a very important person in one of my fields of study. it really helped to solidify some things in my head- things that make sense overall, but somehow the logic behind and interconnections didn’t all come together until i heard this talk. i’m glad i was able to go.
my motivation reserves are low. i’ve become so entwined in the daily grind of completing experiments that i lose track of why i’m here.
i don’t mean that in the justify-your-scientific-existence kind of way. i’ve got my existence justified down to the number of pipet tips i use. in all honesty, i believe very strongly in my research. if i didn’t, i would be spending my time on something i thought was more worthy of the suffering we graduate students endure.
no, i mean what the hell pushed me here in the first place? why graduate school?
this took a bit of deep thinking, but it comes down to an incredible desire for stability in my life. without going into overly personal details, i haven’t had a chance at seeing what a stable, comfortable life is. a life where one isn’t constantly worried about, oh you know, EVERYTHING. and the best way i could think of to avoid continuing that lifestyle for the indefinite future was to get as much education as i could. lack of education leads to low income, low income makes it hard to support a child, a child makes it hard to get an education, so desperate actions are taken. sometimes it’s ok in the end, sometimes it destroys lives. i ran as far away from that situation as i could, which meant college, graduate school, anything to never put myself in those shoes.
at some point, someone will pay me for the things i know and have experience doing. at some point, the job won’t be in constant peril. at some point, i won’t have to skip the doctor’s visit because i don’t have the money, or get by on bread rolls from the back of the freezer for the last 3 days of the pay period.
graduate school sucks, but it is the path forward. someday, my future self will thank me.
things never work out the way you plan them to. especially when you’re near the end and desperate to knock out the last of your tasks.
i am the master of efficiency. i achieve this by having thorough plans for basically every bit of time that would otherwise be downtime. this allows me to juggle all kinds of things and keep everything moving along and making that almighty progress.
so i had a big project planned, and the person who was teaching me the new method underestimated what i could handle on a daily basis, increasing my time spent considerably. we ended up having to postpone that project because, as the rule states, things never work out the way you plan them to. some drug was contaminated, no longer usable, and has to be special ordered. except that it will be weeks before we get it and i refuse to be idle.
so on to plan b: the other massive project hanging over my head. i find myself exceedingly grateful that there was a plan b, and that this was not the last experiment on my list. i would have lost my mind- most likely throwing things and swearing and such.
i did make some progress, though. i learned the new technique and found that i can do the experiment in 4 larger groups instead of stretching it out with 5 smaller groups. and i had time to make up all the reagents for plan b thanks to my scheduling efficiency.
the next few weeks will only be 6 day weeks, but the days are long. each hour, each day, one day closer!
another item crossed off the List.
and you know it’s a big deal when i actually capitalize something. i’m admittedly horrible about caps, but at least i’m consistent. my thoughts are all in lowercase, i think it’s just an aversion to the rest of my proper-punctuation life.
4 main items to go. one done over the weekend, one done next tuesday, and the other two are the reason i won’t have a day off for however many days are left now.
i’m exhausted, and i have many days to go before i get a day off. i’d take a day just to sleep late if my experiments would throw me a bone, but no such luck.
Most of the employers that have budgeted recruitment funds to send recruiters to [university name] this fall will not be targeting Ph.D. Candidates [...] However, a few organizations will consider doctoral applicants as part of their master’s and bachelor’s candidate pool for roles that may include basic research but focus more candidates’ trainability for organization-specific tasks and the application of a wide range of both technical and soft skills.
ok, this concerns me. between nih funding having been in the sewer for how many years now and the economy in general rapidly following suit, it’s a little frightening to see something like this and wonder just how many new phd’s there are as opposed to jobs available for them.
because let’s be honest, all this email really says is “hey, good job on getting that phd and everything, but just so you know you’re competing with people who have bachelor’s and master’s degrees. psst, if you wanted to do that, you should have quit 3 years ago.”
i darkly joked in college that the recession meant it was a good time for me to be in school. but i suspect the economy, and subsequently job opportunities, will be in even worse shape this time around- by the time i’m ready to hit the pavement for real, that is.
i consider myself fortunate to have a couple of good connections and solid references from well established researchers. overall i’m hoping that plus my record and my abilities and skillset find me somewhere desirable. however, no matter how you slice it, this is not the least bit encouraging for someone like me to read.
i finally dug out my graduation present to myself from over 4 years ago: a beautiful diamondback trail bike with every option i could have ever dreamed of. i rode it for about 80 miles, then got too busy with the business of getting married and moving across the country. the formidable heat and humidity of this particular region knocked me right off the recreational trails, and so the bike sat.
horribly depressing, that. recreational biking was once my favorite pastime and greatest stress reliever.
now it sits in my living room after a fresh do-it-yourself tune-up because i don’t have the money to pay a local bike shop to do it for me. it took me a while to get the derailleurs adjusted, and i still have a rotor that’s not 100% true, but that’s $100 i didn’t spend. when you’re on a limited budget, that’s a big number. especially since i took it on a test ride (my body liked it more than walking, and the feeling of riding brought back much happiness) and remembered that i made a poor seat choice for a hardtail. i will be seat shopping soon.
speaking of doing it yourself… i’m at the stage now where i pretty much insist on doing all experimental work myself. it’s not that i don’t appreciate offers of assistance. normally, the instructional time input is greater than my own personal gain in that situation. and with my undergrad minions of days past, the point was for them to get the personal gain and for me to learn how to teach. now, if it takes more time and more energy to teach and supervise to have someone else do it… i’ll do it myself, thanks. i’ll happily give input and assistance to others when they ask for it, but my stuff is mine alone.
when spending several hours in a dark room mounting brain sections to microscope slides, and then spending several more clicking, focusing, clicking, and focusing on a microscope setup… it’s pretty easy to give my mind some time to do its thing. i’ve had some of my best ideas pop into my head while doing these routine grunt-work things, things that require only a certain part of the brain for coordination, but leave the rest for deep thought…
today my mind didn’t snap to attention at new ideas, scheduling panic, where the hell i’m going to find a job halfway across the country. today i thought of the day i walked downstairs to the lobby of the residence hall and saw 15 people gathered around the tiny tv- just in time for a second plane to hit the tower, the billowing smoke, the horrible things that had to be happening inside.
i stumbled to class, unseeing, numb. classes were optional, most of us gathered around the clocktower in grief instead. the mass of students grew as the day wore on, as the night fell candles were lit in the september evening chill. we didn’t notice. though we were very far from our brothers and sisters in new york, we wanted very much to do all we could. the feeling of helplessness that evening was heavy.
my pseudo-big brother got the orders immediately. he had joined the army as i left for college, august of 2001. he needed to straighten his life out, and the army was the way to do it. i didn’t need to hear it, i knew he was first in line to go kick some ass. friends in boot camp prepared for deployment while others immediately transitioned from not knowing what to do after high school to wanting to fight for our country.
but the most stunning, breathtaking thing? these horrible, despicable events brought us together. we put aside our differences, our disagreements, and we worked together. i saw outpourings of human kindness i have never seen before. i heard amazing stories of bravery and sacrifice in new york, incredible generosity from the rest of the country, and brave souls from all over rushed in to help however they could. this is the true america, this is what we’re capable of.
we lost many great people on 9/11 and in the events since. i grieve for all of them, and i hope they are at peace. i hope their families find comfort. america will never forget.
from the mountains,
to the prairies,
to the oceans,
white with foam,
god bless america!
my home sweet home.
today’s number is 65. that’s the number of days i will work, in a row, with no days off. it’s all planned out now, no backing out.
next day off: it’s sometime in november.
i want to throw up just thinking about it. what kind of a mess i’ll be by then is anyone’s guess. then i switch over to a 6 day work week for 3 weeks to knock out the 2nd to last item on The List. the last one, i’m putting off even thinking about that for a while.
i need to tune up my bike and keep it in the back of my car, walking back and forth to various places for these experiments is going to be too much. and i’m going to use this as an opportunity to proclaim my love for my car, i can haul almost anything in it.
wish me luck. the next couple of months are going to be a new kind of hell.
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