Bedside to bench top: My experience as a K-RITH intern

My time here at K-RITH started with an interest on the effects that concentrating a single metabolite created by Mycobacterium tuberculosis in the surrounding lung tissue could have on disease progression. I was developing a protocol to purify and detect this metabolite from tissue since our lab had only previously worked with patient serum. These first weeks could have just as easily been done at any lab around the world, but how it became one of the most incredible research experiences I’ve had was very much dependent on my location at the epicenter of the disease.

Working in Adries Steyn’s lab, I was able to interact with the pathologists and cardio thoracic surgeons at Inkosi Albert Luthuli Central Hospital. Being the most advanced public tertiary care center in the TB rich KwaZulu-Natal area (that serves 11 million people) means there are 5-8 lobectomies per week due to MDR/XDR TB or neglected care. The proximity to a high volume of patients means relatively easy access to not only patient samples but also an understanding of their living environment, health history, treatment regimen, and any further questions can be answered by the surgeons you know personally and are a phone call away. For example, I had the opportunity to meet with the surgeon who had taken out the lung 10 days before and talked to him about why the patient was referred to him, the symptoms he had and how/ why he removed what part of the lung he did. After the 10-day formalin soak the lung lobe was able to come out and cut up for histology purposes. The pathologist explained the macroscopic changes the infected lung had undergone before I got to watch them section, paraffin embed, cut and stain it for histological analysis. After the slides were prepared the pathologist went over them with me pointing out some key histological changes the patients lung had. In the future I would be able to get a section of fresh lung tissue that I could then use to quantify and localize my metabolite. At the same time the surgeon and pathologist could provide patient history and histological analysis/ explanations to the changes present in that specific patient sample.

This opportunity at K-RITH and Adries Steyn’s lab has provides the ability to see the patient’s problem in its entirety: from preoperative rounds, to the surgery itself, then the pathology department and then ultimately using that same tissue in basic science bench work. This is an unparalleled scientific experience that gives me a great idea what’s at the core of translational research and represents exactly the scope and complexity research I hope to accomplish as a future physician scientist. So in many ways, like real estate, location for translational research matters and K-RITH has been a great experience!

Week 4 & 5

On the research side there is an exciting new direction were taking with drug treated and infected mouse lung tissue. More results to follow.

After the safari adventure it was time to spend a weekend in Durban. Durban in July is the largest horse race in all of Africa and it was this weekend. The theme was "Posh? Oh my Gosh!" and it was quite a fashion parade. This also meant living on Florida road - the club district- was like living in a mad house. July weekend had people covering the street and every club packed. It happened to be a girl in our programs birthday so the group of us braved the crowds for a sit down dinner. The venue was nice, food so so, and service was slow, all things to be expected during this chaotic weekend.

The next week at K-RITH I collected infected as well as drug treated mouse lung tissue to examine its metabolite differences. I have been working closely with Jon who's set up the MS for analyzing patient serum samples. His past experience as a professor teaching analytical chemistry has made him an incredible help for my project. With some extensive literature research and Jon's help I had an effective method set up to discover the unknown importance of my particular metabolite in TB infection.

This weekend's trip was to Cape Town. Several lab mates are from the city so of course they shared all the best places to visit. A couple friends were joining me and I  had planned to stay at a hostel in city center. The backpack as it was called turned out to be a lively place and my roommates were from Canada and Great Britain. Since the best way to get around the city was by rental car and the cheapest option was a manual, I had a quick right hand drive lesson with a lady in the lab the day before I left. It wasn't as confusing as I originally thought. When we landed we rented a little Toyota Aygo and were off to explore the city. I picked up one of our friends who had landed the day before and drove towards cape point. The scenery is beautiful beyond description and is definitely a place everyone has to visit. One of the running jokes among south africans is how so many tourists wear khaki pants and hat around the city like their going on a safari. I definitely avoided doing that that but the second joke, that tourists describe cape town almost orgasmically, was harder to avoid. It's definitely a one of a kind place that stick with you.

Day one we visited boulder beach to see the penguins, I had the best Hake (fish) and chips in my life, saw cape point,  the lighthouse lot of baboons, the cape of good hope, drove on the most amazing cliff side road and watched the sunset at Hout bay.

Day 2 we visited Stellenbosch for wine tasting and a city wide festival in Franschhoek with more incredible drives in between. In Stellenbosch we visited a winery called waterford that had the most inviting and comforting atmosphere. It was a typical rainy cape town day but wine and chocolate tasting (apparently the first winery to pair chocolate with wine) in front  a fireplace with their super friendly rhodesian ridgeback (lion hunting dog) made you feel like royalty. That night we checked out long street (entire street with neighboring bars, clubs and quirky shops) for its famous nightlife.

Day 3 we visited Muizenberg for their sunday market and drove to a local township where you buy the raw meat and they braai it for you at incredibly cheap prices (~ 17 ran per kg meat = $1.70). It was probably one of the risker places we visited on this trip but thankfully we made it back with all of our stuff. That night we relaxed before our 6:30 AM flight back to durban.

Note to others: an early morning flight into cape town gives you an amazing sunrise.

Week 3 & 4

Research has been surprisingly smooth sailing up to this point. We've done duplicates with the mouse lung and we know we have a stable quantification method now. Literature research has been unhelpful in trying to figure out if formalin is going to mess up our very expensive columns/MS but after a little pilot experiment we figured its not a good option. Next step is to test a filtering purification system.

During the weekend a group of us planned a safari trip to Hluhluwe-iMfolozi park, a world heritage site. The driver who picked us up was only a few years older than myself and had brought his best friend from high school along for the ride. On the journey he explained how Zulu music today is heavily influenced by House music while listening to some of his favorite CD's. The game park was in Zululand, his hometown, so he had lots of stories about growing up in a commodity rich environment. All along the trip were acres and acres of sugar can fields and gum tree (lumber) fields. Off the in the distance we could see numerous factories he said produced steel, glass, aluminum, lumber and coal. Overall, there are lots of jobs available except they're all unskilled labor intensive positions. His dad was a lumber worker but he had not interest in following in his footsteps.

We arrived at our lodge in St Lucia just before the sunset. The lodge itself was a quant little place with a big park across the street and upon check in they gave us many warnings about walking around at night. This was a normal warning for South Africa except it wasn't crime you needed to worry about, its the hippos. I thought it was partially a joke and partially just an overly cautious warning about something that has happened a couple times before. Turns out it isn't, in fact the park across the street must have tasty grass since a late night star gazing attempt didn't make it more than 3 minutes before we heard a sound of munching in the dark distance. Its surprisingly hard to work up the courage to shine a light on/photograph a thousand pound animal at night when all you can really make out is a black mass in the distance and the sound of something massive not to far away. So a description will have to do. Either way, a night drive, wetland tour and big 5 game drive over the next 3 days showed me plenty of beautiful scenery and animals to make me feel like I was really in Africa.

St. Lucia the beautiful.

Weeks 2

My research at K-RITH is in full swing. Over these last two weeks I've been busy creating a protocol to analyze my metabolite in lung tissue and have been making great progress. I've been able to quantify it in my mouse lung samples and the next step is to check its compatibility with formalin as a sterilizing agent so we can take the patient samples out of the BSLIII lab and submit them on the MS. I've been spending longer days in the lab which means its dark before I leave K-RITH. However, it isnt as depressing as it sounds because our incredibly slow internet means the other interns and I often get together for dinner or socializing.

Friday night at K-RITH is soccer night. Theres a great little bar with turf soccer courts that people from the lab rent by the hour. PI's, postdocs and interns get together to battle it out for the glory. The competition was tough so it didn't take long for  me to realize how out of shape I'd become. Post game is time for beer... I've begin to appreciate the little things that make this research environment so positive: Friday night soccer, cappuccino machine right outside the lab with the friendly chatty receptionist, and a diverse group of interns. All this makes the 10 hour days a pretty enjoyable experience.

The weekend itself started off pretty relaxing with the day spent at the beach and plans to go to a popular club named Origin that night. We lucked out having our bed and breakfast only ~2 km from the ocean. So on the walk to the beach we pass right by the beautiful Moses Mabhida Stadium where some of the games for the 2010 world cup were held. When we got to the boardwalk we had a little run in with a group of monkeys who were playing in the bush. There are always moneys at the beach, but this time it was pretty funny watching some young kids trying to scare them by hoping up and down/ walking up to them only to get scared in return when they didn't flinch. Good free entertainment. After the monkey business we went to lay out on the beach and take a dip in the surprisingly warm ocean. not a bad start to the weekend.

Club Origin is apparently one of the hippest night clubs in durban since so many different people I assked recommended it first. Here I learned that house music is all the rage in South Africa and managed to meet several local DJ's through the IT guy from K-RITH. The night started off great until an overly friendly guy approached me. He grabbed my arm like he wanted a chest bump which i knew was weird and before I knew it he was leaving. In the US something like that would just happen from someone who was just drunk, here it resulted in a disappearing act for my wallet. Only 15 minutes earlier I had taken out cash for the taxi drive home so I immediately knew he had taken it. After telling some of the guys I was with and a security guard we managed to find the guy and pull him aside.When we searched him all the money was there but no wallet in sight. Since it happend in a part of the club not on camera there was no proving it was mine so security had to let him go. Now out a drivers licence, debit, and one credit card I learned there're no friendly arm shakes.

Week 1 at K-RITH: The Introduction

         Life is different south of the equator. I’m not sure I’ll ever grow accustomed to the high walls and razor wire that surrounds every house but people here are very friendly even tho they live with an abundance of caution. For example the Taxi’s around here know to avoid a particular road on our drive home at night because they say it where people get hijacked. Thankfully not far from our bed and breakfast is Florida road, which is full of restaurants and bars. Were told this road is one of the safest in the city, with a security guard at every building watching the cars and area for trouble, but even then we’ve kept our nighttime exploring to a minimum.

        In the last few days I’ve become good friends with a guy named Yehou “David” Gnopo from the Ivory Coast. He’s the kind of guy down to explore town and grab a drink at any time you call. Last weekend was the Top Gear auto show in Durban which apparently managed to sell out every bead and breakfast/hotel in the city including our own rooms.  This conflict in booking had us move out over the weekend so K-RITH was generous enough to provide an all expense paid trip to the 4 star resort of San Lameer  which was about an hour thirty drive south of Durban in the eastern cape. We later found out this this same slight booking “accident” occurred last year as well no one was complaining which had us thinking this may have been a surprise trip all along... and I'm definitely not complaining  We caught a taxi to the bus station around 17:45 to catch our 18:45 bus. The taxi drive through downtown is always chaotic with open air markets and thousands of people everywhere. Whipping out a camera to take pictures is probable not the best idea so no pictures for now. I was definitely on edge the first week with how dangerous everyone says SA can be, but I haven't been pestered yet. So far it seems the best rules to stay safe here are the same everywhere: Don’t bring attention to yourself and dont wander into places that look unsafe. Although waiting at the bus station for an hour after dark felt a little unsafe it was completely uneventful. Its really an insightful experience to be for once an obvious minority.

        When we arrived at San Lameer it felt a little like we were entering Jurassic park.  There was a tall 12 foot electrified fence and razor wire surrounding the entire resort.  Since we arrived at night it astounding how great the view of the stars was. I once again could see milky way in all its glory and I saw for the first time, as a guy named Ted pointed out: the crux or southern cross. Its hard to miss with the brightest orange star I've ever seen. 

  At the resort we got to take several trips to the ocean, play some soccer and lounge around during the day while I read up on some papers. At night we had a braai the South African way with ted’s gourmet burgers, my grilled chicken, the girls awesome side dishes and as much beer and wine as you could drink. We didn’t have Internet for the entire weekend and yet it didn't matter.

          Back in Durban, after our eastern cape adventure (San Lameer), I was moved from my single room with an awesome balcony into a three-person unit with a girl named Venia and a roommate named Tobello. Six other girls in the program live upstairs, which has makes organizing dinner and activities simple after an exhausting lab day, and Goodness (the name of the manager at Erlesmyer lodge where I stay) takes care of us with a cleaned room and fresh towels every night. I’m surviving

           Tomorrow I have my first lab presentation on my project for these next 8 weeks. I’ve had to read quite a few papers these last few days to develop my non-existent infectious disease background into something more useful. The plan is to develop a way to detect an antioxidant level in patient lung tissue using mass spectrometry. I’ll be visiting a local hospital to learn a little about the healthcare system in SA and also working with a thoracic surgeon as they resect TB infected lung lobes so we can bring it back to the lab. Then I’ll be working in a BSL 3 lab to cut up and store it then prepare samples for the mass spectrometer. The great news is we just got IRB approval! Which makes me pretty excited about this medical/basic science project. My PI, Andries Steyn, has been really good so far about making this a learning experience and helping me to really think through the problems facing this project without giving me answers. This is partially because nothing like it has really been attempted in his lab (or any that we know of) but also because its made me learn a lot about searching through many different kinds of primary literature to get everything from background info on mycobacterial redox to metabolite digesting methods for LC-MS.

A bonus to working at K-RITH is being surrounded by the leaders in HIV and TB research, especially when your desk is at the doorway to the director. In just my short time here there has already been several great talks from people from Cal Tech, Harvard and MIT as well as a NIH meeting, which is pretty good company. In the end sheer amount of positive influence and experience that surrounds you makes for an exciting work environment full of unexpected surprises.