Because I spend most of my time on the Left Bank of the Seine, I was struggling to understand many of the places described in The Invention of Paris, by Eric Hazan. The Right Bank has led the city’s growth since it expanded from the Île de la Cité. Today, Natasha and I decided to take a walk down the Grands Boulevards, an area that became outstandingly popular in the 1830s.
We started at Madeleine, named after a church of that name. You could be forgiven for not recognizing it as a church, though! Many false starts characterized the rebuilding of l’église de la Madeleine, with work finally beginning in 1806 when Napoleon Bonaparte decreed that the structure positioned at the west end of the Boulevards district would be a recreation of an antique temple to the Glory of of the Great Army. When the structure was completed in 1842, however, it was consecrated as a Catholic Church. Since a model of the Parthenon was the focus of park next to the university where I worked in Tennessee, I was a little unenthusiastic about the French equivalent. I liked that art had been displayed between columns along the sides, but the grime of the city has definitely subtracted from its visual impact.
Natasha and I continued on our path along Boulevard des Capucines. I had been looking forward to seeing the former mansion of Farmer-General Marin de la Haye (once featuring a roof garden that fed the house plumbing), but we could not discern which of the buildings at this intersection was his home. L’Olympia Theatre was more apparent by a red marquee and a sign for its music hall. The area is so busy with traffic and pedestrians that I didn’t take good photos. Similarly, we passed by the Hôtel Scribe, which housed the first commercial screening of a motion picture (courtesy of the Lumière brothers), without more than a brief pause.
Arriving at the Opéra Garnier, however, gave both of us pause. The Place de l’Opéra is a fairly big square, containing its own busy metro station. Seven substantial roads meet at the the Place, so the people boiling into and out of the metro are interacting with a heavy crowd around the Opéra itself plus a bunch of traffic noise. It is also worth saying, “WOW!” The structure has a substantial presence of its own in the early winter afternoon, with the sun reflecting beautifully from its façade and glinting merrily from the golden statues perched on either end of the roof. I hope I’m not being too obvious to mention that this is the building in which the “Phantom of the Opera” was first imagined. I look forward to a tour when that sort of thing becomes possible again.
As we continued eastward, the Boulevard changed names again, this time to Boulevard des Italiens. Because I remember the Crédit Lyonnais tower soaring above all others in the Lyon skyline, I was curious to see the headquarters they crafted at Paris starting in 1876. I tried to get fancy with my photography when we reached the former headquarters. The building, which occupies an entire city block by itself, has a frontage so huge that my fisheye lens was barely able to capture it even from the opposite side of the boulevard. I wish we could have seen is glass atria from inside.
In the late nineteenth century, the high-class shopping areas of France opted to create “passages,” roofed shopping areas that might be called “arcades” in English. We encountered Passage Jouffroy and Passage des Princes at 11 Boulevard Montmartre (another name for the same road!). Natasha and I were interested in a bit of shopping, so we turned into Passage Jouffroy. It was surprising just how far through the block the passage continued. We found jewelry stores, chocolatiers, art galleries, and even a small museum. We particularly liked the Librairie du Passage, a used book store with a sidewalk sale in motion. We browsed for quite a while, and then we turned to the Marks and Spencer grocery store. It has been surprisingly difficult to find blocks of aged cheddar in French groceries, so we were pleased to find the British chain.
As we passed Rue Rougemont, I was pleased to see a stylish façade and cupola in the corner of my eye from a BNP Paribas in an historic building. We had a little peek at Sacre Coeur at the crest of Monmartre on another of the side streets! Since I love art deco, I had high hopes as we approached the 1932 Grand Rex Theatre. As we drew close enough to see it, though, I could only say, “that is just awful!” The entirety of the Grande Rex Theatre is now swathed in a multi-story advertisement for Samsung mobile phones. I know that businesses must innovate to balance their books, but this seemed a real low.
Natasha and I suddenly realized we had bypassed an important site on our tour, and we retraced our steps a couple of blocks. On a small side road, we spotted our quarry next to Paris Accordéon (open since 1944!). La Esquinita is a small Mexican grocery, perhaps with ties to the Zicatela restaurant on the other side of the same block. Natasha had been in search of chili poblanos, guajillo chilies, and corn tortillas, so we were delighted to find all three in one shop!
I had just two more items on my itinerary for the Grands Boulevards. As we had passed to the east on our promenade, our route had joined with the course of the walls erected around the Paris of the 14th century by King Charles V Valois (definitely not Charles V, Holy Roman Emperor). It was their path that had largely determined the course of the roads upon which we walked. In the 17th century, Louis XIV replaced a fortified gateway through this wall (guarding the road to the royal basilica of St. Denis) with the first triumphal arch in Paris.
As Natasha and I approached the Porte Saint-Denis, the crush of people and the road traffic picked up considerably. In the distance, Natasha pointed to a long line of police vehicles with rotating blue lights. Her sharp eyes picked up a large yellow flag, perhaps indicating a protest associated with the “yellow vests.” She has explained to me before that if one is living as a foreign worker in another country, lingering near activities that draw police is unadvisable. I was under some time pressure to get my photograph of Porte Saint-Denis, and we rapidly scuttled off our route to the north to avoid the press.
I was glad that we got to see the Theatre Antoine on our detour. We moved a couple of streets east where we saw a line of people 100 meters long waiting for entrance to the Lidl grocery. From there, we could see Porte Saint-Martin, a smaller triumphal arch constructed a couple of years after Porte Saint-Denis. While I worked the camera, Natasha pivoted her head to find the nearest Metro station; we did not intend to linger if the protest moved in our direction. We expedited our walk to the metro station and boarded line 8 back to our neighborhood.
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All week long, Natasha and I have been looking forward to the antiques street market at Rue St. Charles. I can waste lots of time looking through musty old books and artwork of questionable quality, and Natasha is keeping her eyes open for a proper nightstand. When Saturday dawned with bright sunlight and warmer temperatures, we saw limitless possibilities in our weekend!
I included a photograph of Rue St. Charles in a previous post. Today’s ramble was a little uncertain in direction, but we assumed that if we headed north from Balard we would eventually find the antiques sales. Sure enough, after we passed the Lidl Grocery, we encountered quite a few market stalls along the sidewalk. I had expected that we would see a good selection of candidates for Natasha’s nightstand, but the furniture items were more diverse at a street sale we attended near the Vanves area (not strictly Paris but on the opposite side of the road from Paris).
Instead, we saw silverware, lots and lots of silverware. Some was proper silver, and some was just plated, but there was rather a lot of it. Clearly people are sick of polishing the stuff! Yes, we saw boxes of books in hefty leather covers, and we were sorely tempted by sausage sellers who… were not selling antiques? I saw plenty of old miscellaneous artwork and some that was reasonably good. It was a nice start to our day, but we didn’t find any treasures to truck home. Instead, we took a walk down the side of the Seine toward Parc André Citroën.
I think of Citroën as one of the high trinity of French car manufacturers: Citroën, Renault, and Peugeot. The fact that my family drove a Renault “Le Car” for years makes it loom largely in my mind. The very first factory producing Citroën vehicles opened its doors in 1919, and it continued in operation until 1975 (follow the link to see some cool historic photos). When the plant finally shut down, it was demolished and replaced in 1992 by a sizeable public park at the southwest corner of Paris.
Our visit to the park came on the first warm, sunny day Paris has experienced in quite a while. The joggers were out in force. As we migrated from the little gardens of the northwest corner toward the main lawn, we saw large numbers of exercisers in all directions. The lawn itself was dominated by a massive balloon; in normal times, we could even take a short ride for an unparalleled view of the city from above. We heard music piped at high volume from the far end of the lawn, and we realized that Parisian gyms have worked out an alternative strategy for lockdown; the trainers have occupied the public parks instead! Squads of young adults were sensibly spaced from each other, working out crunches in time to the bass-heavy music. We were tempted to explore the sizeable greenhouses, but we eventually retired homeward for lunch.
We weren’t through with our adventure, though! Natasha had watched a little history video of the “Petite Ceinture,” a railroad loop surrounding central Paris, and she wanted to explore the part of it open near us. Much like New York City’s “Highline,” the Petite Ceinture is a raised railbed surrounding one of the most beautiful cities on earth. Since trains no longer run this route, much of the circuit has been converted into a jogging track.
We ascended to the railway at Balard tram stop. The 15th Arrondissement link of the belt is only 1.3 km in length, but that’s most of a mile for which we didn’t need to await crossing signals or contest with motorbikes. It was nice to find an open space amongst the buildings at the edge of Paris. I think the elevation gives an interesting perspective on streets that seem quite different from the pavement.
It is worth noticing that informal public art also appears on much of the railway, though the batch opposite what was once a station for the route took advantage of the solid wall there.
As we reached the end of our segment, we were able to pass through a pedestrian viaduct to an entrance for Parc Georges Brassens. We were greeted by one of the hugest murals I have ever seen on the side of an apartment block.
I have to start with the unique person for whom this park is named. George Brassens (1921-1981) was a poet turned singer who crafted some of the most enduring anarchic songs in the French language. I was so charmed by his songs in my high school French classes (circa 1990) that I can still sing some of the choruses today. When my mother-in-law detects someone trying to stir up trouble, she sometimes comments that “he has his big spoon out.” George Brassens was an inveterate pot-stirrer.
We had traveled past this park many times by tram, but from the streetcar it doesn’t look like much. Our visit to the park today entirely changed our perception of it. This is a park that is very well-loved by its community. It seemed that a new surprise lingered around every corner. Let’s start with the vineyard. The Clos des Morillons grape vines surround a hill on the south side of the park (though they were obviously not at their peak in the middle of winter). What appeared to be a pile of brightly colored boxes next to the vines was actually a series of beehives for training people in their cultivation
The sizeable Monfort Theatre, sitting adjacent to the park, rises to a prominent peak over the southeast corner. We strolled to the northeast corner and found a party. Across the lawn, we could see a pretty clock tower and a huge area being remodeled into a huge play fountain. When we first arrived in the area, we heard an unusual bit of public singing from a group of young men in the clock tower. By the time we made it to the other side, though, they had been chased away by a security guard.
Of course I stopped for a moment to have my picture taken with the donkey and his cart. I appreciated that the small carousel had been painted with images of the poet, but Natasha was sad to see that the carousel did not feature a gorilla, but then that song is not really intended for children. We paused to watch a group of young people rehearsing a dance in the pavilion.
Brassens Park also offers an unusual place to relax. A small hillside has been covered in irregular cement “boulders” offering a large number of flat places for a hand, foot, or ample behind. I like Natasha’s photograph of me. The rock heap is a great place to watch the kids’ playground. The “poles” framing one of the structures were surmounted by a couple of sculpted ravens and other creatures. I loved the chaos of all of it! Georges would approve.
As we wandered the route back to our place, we tried to stop at a Latino grocery; we felt we had struck gold when we visited the place for the first time a couple of weeks ago. Sadly, it appears that the place is temporarily closed because serious construction work now fills that store. We turned onto Rue Vaugirard and were thrilled to find ourselves standing in front of another grocery with many of the ingredients we would need to make our Mexican cuisine (albeit adapted by a South African and consumed closer to Spain than to Mexico). Natasha revealed that I could purchase my beloved “malta” at the store, and I nearly cried. Paris is becoming more like “home” every minute.
This morning dawned bright but fiercely cold. Natasha and I slept a little later than we usually do (8:30 AM), but we quickly arose to start our plan for the day. Despite a high temperature of -4 degrees Celsius (25 degrees F), we would do our best to get out and about!
Natasha learned very early after our move to Paris that street vendors can frequently beat the prices of supermarkets for vegetable prices, and some of the co-ops have really excellent selection! We came down to the Saturday street market, just a couple of blocks from our building’s front door, featuring produce, seafood, and even some flowers and live plants. I am afraid we got the direction of the queue backwards, but everything turned out okay in the end. Natasha acquired broccoli, onions, avocados, cauliflower, spinach, and others. The price wasn’t bad, just 17 Euros ($20).
I knew Natasha was ready for some pretty flowers at our apartment, so we walked to the back row where the flower sellers work. The temperature was bracing enough that they were selling the flowers from the back of their lorry, with a heater blowing in. I found Natasha some lovely white roses with tiny purple flowers as accents. I think she will enjoy them!
After dropping our produce back at the apartment, we came back outside for our big trip of the day. I’ve been assembling a home computer to take some of the load off my laptop. Today I was to acquire a new video card and and old scanner for us to manage documents a bit more easily. We took Metro Line 8 across the city. We live in the Southwestern part of the city in Arrondissement 15, but today we would visit the boundary between the 10th and 11th Arrondissements in the Northeastern part of Paris.
Place de la République has gained some fame as a premiere location for mass protests in Paris, and the wide tiled space flanked by two rows of trees truly lends itself to this use. All that flat area with some smooth steps is also a prime attraction for young people enjoying skateboards and scooters. When we emerged from Line 8 at République, a protest was already in progress, with a speaker delivering his address through a megaphone at the foot of Marianne, a massive bronze statue above a sculpture group in the center of the square. The sounds of the rally competed with the racket of dozens of skateboarders taking turns at the Eastern end of the plaza. When we returned to the square just a couple of hours later, the initial rally had given way to another group waving flags in a procession around the base of the statue. The stores facing Place de la République did not look like they would be affordable places to visit.
Natasha has been excited about the opportunity to visit a gluten-free bakery since our last encounter of one in Madrid, Spain. Being at Place de la République gave us the opportunity to visit Boulangerie Chambelland, a bakery a few blocks east on Avenue de la République. We knew we had found the right place when we saw a line of people in pairs a meter apart outside the door. The bakery was allowing only four customers into the shop at once due to COVID-19 restrictions. When our turn came, we had already taken a gander at the goods through the shop window, and our stomachs were growling in anticipation.
Natasha began pointing at items and calling off names. We ordered two long chambellines, one in sugar glaze and one with raisins and vanilla. Natasha selected two focaccias, one with herbs and one baked with olives. We could not resist the allure of a lemon tart with meringue and a hazelnut cream Paris-brest. We exited the store with a bag of goodies and big smiles on our faces.
It was time for us to meet the scanner seller from Le Bon Coin (French equivalent of “Craig’s List” or “Gumtree”). We made our way back to Avenue de la République, but this time we crossed it on Avenue Parmentier, turning right onto Rue Darboy and passing the beautiful Église Saint-Joseph and then the Square Jules Verne. After a quick diagonal on Rue Louis Bonnet, we were at the Belleville Metro station.
It was pretty odd to emerge at Belleville, because we were suddenly in the heart of one of Paris’ two Chinatowns. The area was filled with shoppers and merchants, and a political protest for the Moroccan community was in full swing across the intersection. I didn’t take a photograph, but I think this image by Célia Pernot captures the sense of motion there.
Happily the fellow we were meeting was watching for us, and he carried the equipment over to us at the foot of Le Président restaurant. I handed over the price, and we were soon on our way down the direct route to Place de la République, Rue du Faubourg du Temple.
The area was absolutely packed with shops and shoppers, and we had to stay nimble to avoid collisions. We happened upon Librairie Les Nouveautés, and if you know me or know Natasha, you can be sure that we turned as one to enter the bookstore. I loved the options they had in the history section, but my ability to read French is still pretty halting and limited. It was lovely to be indoors after so much cold air, but we were soon moving southwest toward Place de la République. We paused in the square Frédérick-Lemaître for Natasha to have a snack.
I had some business of my own. With every step I took, I heard a soft knocking inside the scanner. I think people may not know that when you ship a scanner, you should always lock its scanning bar in its resting position. That knocking I heard was the scanner head getting moved by each bang against my knee or from my swinging my arm holding the bag. I soon had to carry the bag in my arms like a baby because the hand holds of the bag ripped through. I didn’t successfully get the scanner head locked into position for another hour!
Natasha and I had decided our Valentine’s dinner would come from Tasca, a restaurant of Italian cuisine that makes only gluten-free dishes. When we re-boarded Metro Line 8 at République, we were on our way homeward. We resisted the sweet allure of home by exiting at La Motte-Picquet – Grenelle. People familiar with Paris will know that we were now in tourist central, quite close to the Champ de Mars that stretches from l’École Militaire (Napoleon Bonaparte attended as a student when the school was thirty years old) to the Eiffel Tower. We walked some distance down Rue de Suffren and soon found our restaurant.
I may not have said it in so many words, but I must admit Paris is expensive. I had worried that this specialized restaurant would have a tremendous bill, but I should not have worried. The restaurant was running a special: two cannelloni ricottas or two lasagne bolognaises for just 10 Euros. Natasha and I conferred, and we asked “why choose?” We soon were on our way back to the Metro with a bag full of pasta and even breadsticks.
This afternoon required a stroll into the city; new parts for my home workstation were ready for pickup! Natasha and I took the opportunity to see a bit of the fifteenth arrondissement, soon to be our home.
If you haven’t heard the word “arrondissement” before, it is a term worth learning before you visit Paris. The historic city center is divided into 20 of these districts, with the 15th (sometimes called “Vaugirard”) being one of the outer ring segments on the “rive gauche” (left bank) of the Seine.
Since our temporary home is the Cité Universitaire, Natasha and I needed only to scoot westward around the Boulevard Périphérique, a busy road that replaced the 19th century “Thiers” walls surrounding Paris. I acquired four tickets for public transport (they are usable on busses, trams, subways, etc.), and we quickly caught a ride west. We popped off at a stop called Balard, ducked under a rail bridge on the north side of the tram route, and soon we were on the Rue St. Charles.
Paris may be famous for its boulevards, but I would say that I have often wished that the city had a sensible grid layout like the cities in the Midwest where I grew up! Rue St. Charles had the lovely property that it ran straight and true from the tram stop to the computer store where I would pick up my parts. I had hoped we would have a nice view of Parc André Citroën (named after the industrialist who founded a French car company), but the closest we got was a view of the Esplanade Max Guedj with these colorful triangular pavilions.
The French boulevard system is useful to tourists because the great streets typically run between major monuments. The perks of following St. Charles north were soon apparent as the Eiffel Tower appeared in the distance.
Rue St. Charles became a bit busier as we approached its intersection with Avenue Emile Zola. In fact, the Place Charles Michels at that intersection offers the only carousel I have ever seen at a McDonald’s restaurant! We doubled back, realizing we had traveled a block further north than we had planned. I am glad we did, because we found a grocery store celebrating my niece.
At that point, we were only a few steps away from the LDLC boutique. I placed my order two days ago, so I was happy to get their notification that my parts were available this morning. After standing in the wrong line, I was directed to retrievals, and in no time I had a big box that barely fit our shweshwe shopping bag. It seemed a little oversized for an SSD drive (40€) and a wifi PCI-Express card (14€), but these are the times we live in.
Natasha had crafted our return path to continue east along Rue d’Eglise (“Church Street”). Our path took us to Square Violet, named after an 18th century statesman who developed this area of the rive gauche. It looked like a thoroughly pleasant place to take a walk.
Of course, having been promised a church by the name of the street, I was determined to find it namesake! We continued east to the Félix Faure metro stop, and my curiosity was answered. We were looking at the back side of the Church of St. John Baptist de Grenelle, dating back to 1827.
This was our big turn to the south. We followed the Street of the Morane Brothers south-southwest past a small public water fountain until it merged with Rue de la Croix Nivert. When we encountered a café at Rue Lecourbe, Natasha patiently waited for me as I indulged in my favorite treat, a pain au chocolate (essentially a light and flaky croissant wrapped around two pieces of chocolate).
We were almost home and dry. A few more blocks brought us closer to the periphery road, when suddenly I stopped dead in my tracks. The blue piece of paper lying on the sidewalk between my feet was unmistakeable. I bent forward and picked it up. It was no hallucination– in my hand I held a twenty Euro note (worth ~$24 USD)! I quickly looked around me. Could someone have dropped this just moments ago? I saw nobody fumbling with a wallet, and really Parisians generally look like they’re in a hurry to get somewhere. What should I do? My thinking was practical– where would it make a difference? I spotted a homeless person just a block ahead of us, and Natasha followed my lead. The fellow seemed a bit shocked but then joyful. He didn’t seem to mind that my spoken French is atrocious.
We walked a couple blocks more and arrived at the tram station just in time to catch our ride back to the Cité Universitaire. It was a well-spent two hours.
A special kind of magic occurs when we emerge from a subway station to one of the most famous sites on earth. Natasha and I had decided we would spend this weekend on some long-awaited tourism, and awakening to a picturesque snowfall did little to dampen our spirits. We soon set off for the Latin Quarter, taking the RER B train from the Cité Universitaire a few stops to St. Michel / Notre Dame.
Just like the subways, the RER B is underground, and it’s pretty deep since it crosses the Seine River just after our stop. We had a few escalators and stairs to return to ground level, but when we emerged, we immediately understood where we were, because the façade of Notre Dame Cathedral loomed massively against the snow-filled sky! We of course felt the same pressure to pause and stare as everyone else, but then we were at a crowded corner of pavement between the street on the “rive gauche” of the Seine and the Petit Pont (bridge). We crossed the street and sheltered near the Shakespeare and Company book shop.
Having begun reading Paris, by Julian Green, I was determined to take in the view of Notre Dame from the Square René-Viviani, which adjoins the St. Julian the Poor church. Oddly enough, St. Julian and Notre Dame churches were constructed almost simultaneously (1170 AD and 1163 AD, respectively). The only Parisian churches still standing from an earlier period are St. Germain des Pres (parts from 990 AD), St. Martin des Champs (parts from 1067 AD), and St. Pierre de Montmartre (parts from 1134 AD).
The Square René-Viviani where we stood has developed a rather interesting set of stories. Its rather odd fountain dates from 1995, but the locust tree standing near the church, surrounded by a circle of stone, is reputedly the oldest tree planted in Paris, dating from 1601. One can see a fair amount of stone rubble and ruins in the square. Some of these are rubble left here from the 19th century refurbishment of Notre Dame. On the west side of the church one can find a Roman paving stone!
We continued our stroll down the Quai de la Tournelle, but we turned to the right at the Institut du Monde Arabe. I would say that we chose this route because we were interested in the Sorbonne University campus adjoining it, but we really chose the path because it would shelter us for a few blocks under an overhang of the building! We turned to the southeast to make our way to the Jardin des Plantes.
It was a relief after three weeks of uninterrupted urban living to turn into the green space of the Jardin des Plantes. Perhaps a European or American reading this will think my next statement a bit weird, but my experience of living in South Africa caused me to feel shock at the size of the tree trunks we encountered in the garden. Considering that the royal garden was first created in 1635, these trees have had opportunity to grow quite large.
Natasha and I climbed the spiraling path to the gloriette de Buffon. Some of the snow had melted on the ground, creating a treacherous surface. We waited for a moment so that some couples and families could depart the little gazebo at the top of the mound. We could relate to the adults who were gingerly testing their footing with each step down the stairs. By contrast, the teenagers and kids hardly stopped launching snowballs at their parents and each other as they dashed about! The view was perfectly lovely, even if we couldn’t see very far due to blowing snow.
As we moved into the next section of the Jardin, we passed between two green houses to arrive on the massive esplanade before the Museum of Natural History. Since we couldn’t see very far, it seemed that the field behind us stretched to infinity. Like all other museums, however, this one was shuttered due to the COVID-19 pandemic.
I paused in the snow shadow of the massive museum to plan our next steps. We wanted to see the grand mosque of Paris, which we remembered was in the neighborhood. After a couple of minutes, I declared that we needed to look on the opposite side of the road, just a bit toward where we had entered the park. We walked around the corner of the building and immediately it was obvious that we were looking at the mosque! In my photo, the minaret is peeking up behind the central dome of the building. When we passed the building along Rue Daubenton, we got a better look at the minaret. It seemed to me to have been transported from North Africa. It was simply beautiful.
Having described a broad outline of the Latin Quarter, we realized we had hardly scratched the surface of this historic district. I am still looking forward to visiting the Arènes de Lutèce, the Panthéon, and the Jardin du Luxembourg (to say nothing of the museums the area offers). Still, we were proud of ourselves for our adventure on foot. We retired to our temporary housing by a subway followed by a streetcar.
On January 4th, 2021, I started my new job. A year ago I would not have guessed that my next position would take me to a new continent and a new language! This post explains how my wife and I decided to move north to Paris, France from our home in the Western Cape of South Africa.
I would start by discussing the “push and pull” of my employment at the close of 2020. As I wrote in my prior post, my five-year contract at Stellenbosch U could not be renewed due to financial constraints at the university and national level. Other universities in South Africa were interested in bringing me aboard, but none of them had a pot of money ready to fund that effort. If I wanted full-time employment in academia, I needed to show some creativity in finding the opportunity.
Thinking outside the box
In mid-2020, I encountered a Twitter post from the Institut Pasteur in Paris, France. The Mass Spectrometry for Biology Unit sought to hire a research engineer in bioinformatics. I found myself hoping that a team planning to build their bioinformatics through a staff hire might also welcome a senior partner who could help introduce the peculiarities of mass spectrometry. I asked my wife if she would consider living in Europe for a bit, and her adventurous spirit rendered an immediate “yes.” I wrote a cover letter to Julia Chamot-Rooke, the head of the MSBio laboratory since 2012, asking whether I might serve as a “visiting scientist” with her team for a period of a year. Happily, she replied quickly that her team was interested.
It took longer to elaborate the “how” once we had established mutual interest. I would have liked to arrange this as a “sabbatical,” suggesting that I was on leave from Stellenbosch University in order to acquire new skills that I could introduce to Stellenbosch U upon my return. With my contract expiring, though, there was no indication that funding would exist to allow my return to SUN in 2022. We next thought that I might be a “visiting scientist,” but it appears that funds to support these academic exchanges are no longer available within Pasteur. In the end, we opted for a “chargé de recherche expert” title, which is essentially to say that I will be a post-doctoral researcher (with eighteen years of experience since my 2003 Ph.D.). My goal was to achieve a salary that would cover the rent (Paris is pricey), and Dr. Chamot-Rooke was able to exceed that goal.
Indulge me for just a moment to ask a question that makes me tense: “am I still a professor?” In 2005, I became an Assistant Professor at an excellent university in Tennessee, and in 2011, I was tenured and promoted to Associate Professor. In 2015, I became a “full” Professor in joining the Faculty of Medicine and Health Sciences at Stellenbosch. In 2021, have I effectively “restarted the clock” to become a post-doc? It would be wrong for me to claim that I am a Professor at l’Institut Pasteur. I suspect I will use the phrase “visiting scientist” regularly, to reflect that this is a short (twelve month) appointment. I believe I can still use the title “Professor,” but that flows through Stellenbosch University, not Pasteur Institute.
To grow is to accept new challenges
We often think of our careers as a steady rise in the titles we achieve. I was a graduate student, then a doctoral candidate, then a post-doctoral fellow, then an assistant professor, etc. I would argue that times like today’s COVID-19 pandemic will look like an asterisk on everybody’s curriculum vitae. All of us are struggling to teach or to learn, and all of us find that words flow from our keyboards more disjointedly than ever before (note my nearly nine-month hiatus in writing new blog posts!). I could “retire” from Stellenbosch and work on a book idea or two; really I long for that kind of rest! Instead, I feel the best way to grow in 2021 is to take on new challenges that will make me a better researcher / healthier person / caring husband / etc. What are the types of growth that I hope to achieve from my time at Pasteur?
Learn skills for an emerging type of proteomics
Almost all of my first- or last-author publications from the last twenty years have emphasized “shotgun” or “bottom-up” liquid chromatography-tandem mass spectrometry (LC-MS/MS) data from complex mixtures of peptides. Over that period, the field has absorbed many researchers from other areas, and a bottom-up proteomics user can choose from a substantial collection of well-developed software workflows for developing information from their experimental data. “Top-down” proteomics technologies do not make use of proteases to chop proteins into peptides prior to mass spectrometry. These methods have been developing alongside bottom-up methods, but the number and diversity of software tools to handle identification of such spectra and manage the statistical issues of these matches have lagged behind the bottom-up world. I believe that I will be able to make a valuable contribution by crafting a manuscript of technology assessment for top-down proteomics, asking questions such as “if different top-down instruments analyze aliquots of the same sample, how much do the data overlap?” or “If different software tools are used to analyze the same data files, how much do their identifications overlap?” Having written several papers on repeatability, reproducibility, and quality control, I see many opportunities in the top-down space.
Give back to a country that contributed to my early growth
I was a Sturgis Fellow at the University of Arkansas during 1992-1996, and I was presented with the opportunity to work with Jean-Jacques Madjar, Jean-Jacques Diaz, and Thierry Massé at the University of Lyon during 1994. Those researchers invested in me, but I feel disappointed in what I was able to give them in return. I was deeply uncomfortable working on the “bench,” and I neglected to arrange the proper type of visa to allow me to develop my project more than a couple of months. Frankly, I was so inflexible and shell-shocked at being away from the United States that I’m just embarrassed at how I managed myself. I have always wanted to do better for France, and this year will give me the chance to do that.
Develop skills in the French language that will let me reach a broader audience
My French skills were developed through two years in high school and two years at university. At one time, I considered adding a minor in French to my degree program. I think that after a year in France, I should be able to carry out a basic conversation without becoming lost. My “stretch” goal, though, is that I would be able to teach bioinformatics in French. If I can reach that level, I could help introduce bioinformatics to students in Cameroon, Tunisia, Morocco, or the Ivory Coast, among others. We know that people who initially speak a language other than English are at a disadvantage in science careers; I would like to make science careers more accessible to francophone students in Africa.
Lose my COVID-19 belly
Like many people, I gained a lot of weight during the “lock-downs” against COVID-19. I was still putting food in, but I wasn’t expending energy by walking from one campus building to another or wandering around a shopping mall. My wife and I have decided that we will forgo driving a car during 2021. Unlike transportation in the outskirts of Cape Town, public transit in Paris is very well-developed (metro / busses / trains). I know that I will benefit from “hoofing it” home with a backpack full of groceries.
I love travelling (unlike my younger self), and I hope that we will find some holiday time to visit other major sites in and around Europe. To see Rome again, visit friends in Denmark or Germany or the U.K., or perhaps even fly to Iceland would be much more difficult if we were starting our trips from South Africa.
I am typing these words at Paris in the first week of the new year. May 2021 be an adventure worth remembering!
I started this blog to explain my decision to leave the United States and to move to South Africa. Now it is time for me to say a fond farewell to Stellenbosch University, my academic home for these “fantastic five years.”
I want to thank the people who made it possible for me to come to Stellenbosch U. The South African Medical Research Council teamed with the Department of Science and Technology (now the Department of Science and Innovation) to contribute 60% of the funds required for my five year contract, and the Dean of the Faculty of Medicine and Health Sciences agreed to contribute the other 40%. Gerhard Walzl, now the head of the Department of Biomedical Sciences at the Faculty, marshalled these resources to make my coming possible. After I arrived, he had the challenges of managing me, too!
You might ask why this contract must come to an end. The reality is that money is very tight in South Africa. Business growth was barely keeping pace with population growth when I arrived, with continuing “load shedding” power cuts undermining the economy. In a recent audit of government spending, only 100 of 421 government bodies achieved “clean” audits; money that should have been invested in national infrastructure was spent in dubious ways. South Africa engaged in a largely successful response to COVID-19, but there’s no question that lockdowns had punitive effects on its economy. In academia, researchers who were able to cover much of their salaries through grants had far more job-security than those who were not (and I have definitely not prioritized grant writing while at Stellenbosch). The academic job market at the close of 2020 is a tough one.
I will write another post about my plans for 2021, but this post is intended to look back at my time with Stellenbosch. Is it all celebrations, or do I have regrets?
From Strength to Strength
I have repeatedly been inspired by the researchers with whom I have worked at my three main universities. I would particularly single out the “SARChi” Research Chairs at Stellenbosch University, the University of Cape Town, and the University of the Western Cape. South Africa designed an incentive funding program to retain South Africans in-country who might otherwise have moved to nations with more developed economies. I haven’t met a “SARChi” whom I didn’t admire.
I would also say that the junior investigators at Stellenbosch and elsewhere are a strong group, too. At UWC I would highlight Bronwyn Kirby and Ashwil Klein; Dr. Kirby “rolled out the red carpet” for me to teach essentially whatever topics I would like, while Dr. Klein always has a new idea for building the use of mass spectrometry at his institution. I will really miss the Immunology crew and the crop of up-and-coming post-docs in Human Genetics and TB Genomics. The wealth of skill in my colleagues throughout the Cape Town metro was always a source of inspiration for me.
Teaching the World
Upon arrival in Cape Town, I was unsure who my students would be. I knew that coursework figured heavily in the “B.Sc. Honours” year, but M.Sc. and Ph.D. students did not typically attend classes. For someone who loves being in front of a class room, it was hard to hear that I would have just a few lectures each year. That said, I’ve offered a variety of courses to all comers, from the week of bioinformatics each year in honours to a once-a-week program to teach the Python programming language. When my program officer with the SA Medical Research Council told me she wanted me teaching as broadly as possible, though, I began talking with postgraduate programs at UWC and (Stellenbosch rival) University of Cape Town about teaching opportunities. UWC, as I mentioned above, has had an endless appetite for classes; in 2019 and 2020, I was teaching a week of bioinformatics, three lectures for sequencing informatics in their Next-Generation Sequencing module, two or three lectures in the Proteomics module, and almost all of the Clinical Biomarkers module! While working with Nelson Soares at UCT (he has since moved to the University of Sharjah in the UAE) I enjoyed our monthly “big show” for the community proteomics meetings, and I gave occasional lectures to their honours program, too.
One of the happy accidents of such broad teaching was that I was able to record instructional videos of almost all of these classes. Last year I assembled an index to the YouTube videos and slide PDFs that regularly draws more page views than all my other blog entries put together. I have been grateful to present workshops in other African countries from this exposure. So far I have taught in Ghana, Malawi, and Namibia, but I fervently hope to arrange workshops in Ethiopia, Mozambique, Botswana, or… well, practically anywhere!
This section would not be complete without my praising the students who have chosen my lab for their B.Sc. Honours, M.Sc., or Ph.D. programs. Again, while some of these postgraduate students were at Stellenbosch U, I also served as co-supervisor to students at other universities, even a pair of M.Sc. students at the U of Malawi College of Medicine in Blantyre! Just like the best students I knew back in the States, these postgraduates frequently pushed me to learn new techniques and application areas; to give one example, a 2020 UWC B.Sc. Honours student wanted to work in GI disease, so we framed a challenging project in celiac disease, a first time for me as well. She did an amazing job with it! Just a couple weeks ago, I attended the Ph.D. graudation ceremony for Marina Kriek, a researcher who joined my team after working in industry. I am very grateful for the chance to work with such talented individuals.
Linking South Africa into Global Networks of Molecular Biology
South Africa is a very cosmopolitan place, with postgraduates frequently accepting jobs in Europe or America. Many of the professors who rise to high leadership positions have experience working at institutions in the Global North. My experience with global mass spectrometry, however, had left me something of a blind spot for proteomics research within South Africa. I would highlight two different projects during my time with Stellenbosch that I hope will increase the awareness of what South Africa has to offer on the global stage. After living in South Africa for two years, I had gotten to know researchers at mass spectrometry laboratories across the country. At the invitation of Ron Orlando, a team of us crafted a manuscript describing the types of challenges associated with establishing mass spectrometry facilities in the developing world. Writing a paper with colleagues from six different institutions was challenging, but I was delighted with the result. Our product was later selected as the paper of the year for the Journal of Biomolecular Techniques (the journal of the ABRF)!
In 2019, we were able to make another stride forward into the international community when the Human Proteomics Organization (HUPO) Proteomics Standards Initiative (PSI) held its annual workshop in Cape Town. At first, I was unsure how many of my colleagues would make the trip to the southern tip of Africa, but our attendance was really solid, and many South African graduate students got to network with leaders in the field of proteome informatics. Since this was the first science meeting I had ever organized, I was thrilled with the result.
Emerging Research Interests
Scientists, like all people, can fall into a rut if undisturbed. I have spent the great majority of my career publishing on the identification of peptides, proteins, and post-translational modifications from tandem mass spectrometry data. It’s been a lovely “rut!” Coming to South Africa, however, meant that I would need to broaden my thinking to handle a broader array of bioinformatic and biostatistical challenges. Could I help people accustomed to manual interrogation of flow cytometry data begin using more automated techniques for gating? Could I automate recognizing DNA sequence variants through high-resolution melt curves? While I made some starts in these two directions, the challenge that has been consuming most of my concentration recently has been this: how can we conduct “functional genomics” (transcriptomics or proteomics) in non-model organisms without well-established genome annotations? After substantial work in Salvia hispanica (chia), Crocuta crocuta (spotted hyena), and Hermetia illucens (black soldier fly), I finally feel I have enough answers to pen manuscripts. I have enjoyed asking myself again just what I find interesting!
Pangs of Remorse
Just as there are no perfect people, there are no perfect jobs! I have plenty of reasons to have enjoyed the last five years, and I hope I’ve been able to convey that above. I have, however, experienced a couple of sticky points that have bedeviled me.
Shaken to the Core
Because my professorship was primarily funded from external sources, I was named as a “Research Chair in Proteomics” for Stellenbosch University. I interpreted that title as making me responsible for seeing proteomics technologies deployed as adeptly and as broadly as possible. I sought to establish a solid relationship with the Central Analytical Facilities, which operated the Proteomics Laboratory of the Mass Spectrometry Unit at the Faculty of Medicine and Health Sciences. Seeing that the Proteomics Lab relied on several external USB hard drives as backups, I built a file server for their exclusive use from one of the heavy servers I had brought with me from the States. I offered my services to help researchers who had produced data in the Proteomics Lab get the most information possible from those experiments. For those first few months, I felt we were well-positioned to see real growth in mass spec-based proteomics.
I had become aware, though, of some challenges that caused some potential mass spectrometry users to walk away from the Proteomics Lab after initial pilot experiments. These challenges were not unusual ones for core facilities. They related to reproducibility and comparability, prices for services, experimental sensitivity, etc. I briefly spoke with the head of Central Analytical Facilities at an impromptu meeting, and he recommended that I put my suggestions for how CAF Proteomics could be improved in writing. Halfway into 2016, I wrote a four-page letter detailing ways that my division could work with the Proteomics Lab to improve “takeup” of proteomics at our university. Well, my relationship with CAF immediately cratered. To give a very concrete example, my Proteomics Laboratory key was reclaimed the very next day. I was the Research Chair for Proteomics, but after the mid-point of 2016, my ability to work with the Proteomics Laboratory at my own campus was at an end. I never really recovered from this loss.
No Job is Finished…
Something I hadn’t truly appreciated about my previous institution (an excellent university in the state of Tennessee) was the degree of staff support we enjoyed. As an assistant professor there, I and a handful of other professors were supported by an administrative assistant. When I wanted to write a grant, our department had its own grant coordinator. Even as a new assistant professor, I had my own individual office, with space adjoining it for my lab team. It is important to understand that a grant awarded to a professor is split into “direct costs” (monies to fund the research directly) and “indirect costs” (monies to keep the lights on). At my former institution, an NIH grant of a million dollars would be accompanied by indirect costs of $600,000, reflecting an “facility and administrative rate” of 60%.
NIH grants are frequently won by professors at Stellenbosch University, but their “facility and administrative rate” is locked at 8% because we are not an American university. As a consequence, departments at Stellenbosch are much less able to support a large number administrative staff. A large load then falls on individual staffers for handling issues such as travel reimbursement and shared equipment loan (such as the tabletop projector for the seminar room). I would particularly like to mention Trudy Snyders, the senior secretary for our division, who demonstrated great patience with me on many occasions. The Faculty of Medicine and Health Sciences does have a Research Grants Management office, but a substantial amount of grant proposal help within our division came from the generosity of Helena Kuivaniemi, a professor with unflagging energy. Until the final year of my contract with Stellenbosch, our division occupied two floors of the aging physiology and anatomy (Fisan) building, with space at such a premium that even some SARChi Chairs were sharing a room with other lab heads. At the conclusion of 2020, I was able to see my division happily taking up residence in the new Biomedical Research Institute, a huge upgrade in its infrastructure.
All in all…
I was very lucky to have these five years with Stellenbosch as a time to reinvent myself. Living in these beautiful surroundings, working with people I admire, allowing me to tinker with new possible directions for my research was a genuine gift. Some cynics back in 2015 told me I would regret moving myself across the Atlantic, but I wouldn’t give up this time for anything. Stellenbosch has made its mark on me.
I decided to group together Swope and Benjamin to reflect their shared resting place. When Swope Park was first dedicated as a public park in 1896, the land was four miles south of the city limits. Today, the park falls within the I-435 loop that surrounds the Kansas City Metroplex. The park has gradually gained more amenities over time. It is home to Starlight Theatre, the Kansas City Zoo, and the Lakeside Nature Center. The area had only been a park for thirteen years, though, when the donor of the lands passed.
Thomas Swope came to Kansas City in his 30th year. He proved to be a very shrewd land investor. On April 16, 1857, Swope re-sold a valuable tract of land to the city (near 10th Street and Grand Avenue), one of the early expansions of the city’s original boundaries. Despite Swope’s involvement in large-scale land investment, he remained a very private man, eventually moving to occupy a room in a family mansion at Independence, Missouri. I am sure he would have been mortified that his death in 1909 became such a public scandal. Dr. Bennett Clark Hyde, the husband of his niece, had served as Swope’s doctor in his final illness, and the man was brought to trial for the murder of Thomas Swope. Three trials for Thomas Swope’s murder followed. Thomas Swope’s body only arrived at its memorial in Swope Park in 1918, and the memorial construction continued in three different phases of construction until 1931. It incorporates a mausoleum and colonnade (begun in 1917), a fountain and balustrade (begun in 1922), and a gate and stairway (begun in 1930). Rob Scott‘s photograph of the memorial appears at the top of this post.
Alfred Benjamin came to Kansas City with his family in 1880 to launch a branch of the Abernathy Furniture Company. Benjamin rose to prominence, serving as vice-president of the company, and in 1905 he became president of the United Jewish Charities. Benjamin demonstrated a clear desire to help those in poverty, regardless of religion or race, and he donated a substantial portion of his own income to the cause. At his death in 1923, both Catholic and Jewish leaders spoke in his memory. Four years after his death, the memorial beside the road to Starlight Theatre was completed. The statue and fountain illustrate the principle he lived by, that those with much should contribute to the welfare of those who don’t have as much.
The Pendergast Machine dominated Kansas City politics for the first four decades of the twentieth century. “Alderman Jim” set the stage for his brother Tom’s domination, serving nine terms as alderman on the city council. His populist political style won him praise from the Kansas City Times obituary writer: “his generosity, his big-heartedness, his readiness to do favors for the ‘boys’…” By the time his memorial was dedicated in 1913, however, Prohibition had changed the appraisal of Jim Pendergast; his ownership of a saloon made him a participant in “an unnecessary business and a bad one” (Kansas City Journal-Post).
It may be unsurprising, then, that his memorial has had a checkered history. The monument shows him seated in a throne-like chair with flanking statues of youths with animals. The memorial started life in Mulkey Square Park, south of W. Twelfth Street, but the 1965 Crosstown Freeway project put it in storage for a while before it was replaced in the reshaped park. Whether James Pendergast was confused with his brother Tom or for another reason, the memorial has been a frequent target of vandals and thieves. Within a few years of its 1913 dedication, people had swiped the two flanking youthful figures (recast in 1916). In March 1933, the arms of the flanking figures were cut away. More damage followed, so that even the bronze panels showing the accomplishments of Pendergast were removed. Despite these challenges, the James Pendergast Memorial has been reconstituted. In 1990, the memorial was shifted to its current location at W. Ninth and Jefferson.
The vocation of William Volker would not seem hugely profitable, but his business in wholesaling picture frames led to a business selling window shades and soon other home furnishings. The Volker company eventually was able to open branches throughout most Western cities. Holding aside one million dollars for his wife’s benefit, he otherwise contributed tremendous sums of money to philanthropy on the large scale and to individuals. William Volker granted the land on which the main campus of University of Missouri– Kansas City was constructed, and he also launched the Research Medical Center.
Piland and Uggucioni spend twelve pages of their book describing the development of the ambitious fountain celebrating William Volker. The puzzling character of Swedish sculptor Carl Milles delighted me. The principal subject of the fountain is Martin of Tours on horseback; the saint is known for having sliced his cloak in half to help a destitute person. Milles’ sense of whimsy really comes through in his sculpting a wristwatch on one of the angels! Carl Milles died in 1955, so he was present only in spirit for the fountain to be inaugurated at Theis Park in 1958. I have frequently driven past this enormous fountain in its second location on the south bank of Brush Creek. You can be sure I will stop to get a closer look the next time I visit my home town!
I could have sworn that the last fountain in this post was simply “the Kansas City Fountain” or “the Plaza Fountain,” but this probably reflects just how important J.C. Nichols was to the development of our city’s design. Many architects in our area were influenced by the City Beautiful movement of the 1890s and 1900s. J.C. Nichols was a pioneer in designing urban projects that make room for automobiles. In 1908, the Kansas City Star gave a useful summary of his intent with what became the Country Club Plaza:
A general plan has been adopted by which boulevards, winding roads, stone walls, rustic bridges and circular drives, shelter houses, systematic planting of trees and shrubs, the creation of private parks, the treatment of running streams, work out into a harmonious whole. The old method of laying out in squares regardless of topography is abandoned and the property is so divided as to permit intelligent treatment of hillside or lowland, thus escaping any ugly unsightly cuts or fills.
The Plaza is an obvious place to visit for almost anyone who comes to Kansas City for the first time. Unlike most parts of the city, the Plaza has a very unified Spanish architectural style, taking its pattern from architect Edward Delk. The 1923 Tower and Mill Creek buildings set the stamp that would influence the design of all other commercial buildings nearby. By 1967, Kansas City had become “sister city” to Seville, and it constructed a small replica of the Giralda tower at the Plaza.
I was quite surprised, then, to discover that the iconic Plaza fountain celebrating the life of J.C. Nichols was in fact created for the Mackay “Harbor Hill” Estate in New York by Henri Greber in 1910! The vandalized and dismantled fountain was purchased by the Nichols family in 1952, just two years after the death of J.C. Nichols. A local sculptor, Herman Frederick Simon, created plaster models to replace the heads of the two children riding dolphins. A monument for the Daughters of the Confederacy was moved from the Plaza site to make room for the new fountain. Construction could only begin once the necessary funds had been raised, and so dedication of the fountain could not take place until May of 1960. In 2014-2015, the fountain was refurbished at the cost of a quarter million dollars. Two months after this blog was originally posted, the Black Lives Matter protests in the aftermath of George Perry Floyd, Jr.’s death elevated public awareness of J.C. Nichols’ efforts to segregate neighborhoods, making his homes available only to white families. In June of 2020, the mayor of Kansas City and its Parks and Recreation committees were debating plans to rename this fountain!
The 1803 Louisiana Purchase nearly doubled the area of the United States. Settlers were soon on their way west to claim farms and trading sites throughout the Purchase, often using the Mississippi and Missouri Rivers to speed their travel. This blog post will examine the settlements near the bend of the Missouri River to answer a basic question: why did Kansas City become the largest city in Missouri?
Missouri as a launching pad
Today, we have any number of options for long-distance travel. It would seem no remarkable feat to travel to a city many states away by jet, and reaching another city in the same state is generally a simple matter of driving a car for several hours. In the days before railroads, however, rivers were necessary for speedy bulk transport. The pioneers who established trade routes to Spanish / Mexican territory, Mormons who sought a place to practice their religion in peace, French fur traders who needed to ship their goods east, gold miners bound for California, and others saw the Missouri River as the natural route. The National Park Service illustrates this neatly with their map of the National Trails System.
In 1808, five years after the Louisiana Purchase, the federal government sent cavalry from St. Charles to construct Fort Osage near the Missouri River to extend its reach into the vast region and to protect a “factory” for the fur trade. The Osage Indians conducted an active trade with the fort, and they were willing to host missionaries from the United Foreign Missionary Society, which operated the Harmony Mission until 1837. The factory at Fort Osage, however, competed with the private fur trade, and it shut its doors in 1827. While Fort Osage was the first American outpost in the area, it did not nucleate a city.
The French fur traders had established networks across the Purchase in advance of its sale to the United States, and they continued their activities after its annexation. The Chouteau family ran the American Fur Company from St. Louis, Missouri. The family used formal marriages to solidify their grip on the trade, and they frequently established common-law marriages with women from native American groups to solidify trust relationships with them. Francois Gesseau and Bereniece Chouteau may reasonably be called the first settlers of what is now Kansas City, arriving in 1821. After his initial fur trading camp was washed away in the floods of 1826, Francois established a home and warehouse on higher ground at the Randolph Bluffs. “Chouteau’s Warehouse” became a key depot and boat-to-wagon transition site. While a dozen other families joined in the settlement, it remained largely a commercial site, growing in value especially after the Fort Osage factory was discontinued.
For the first few decades, Independence, Missouri looked like it would be the dominant city of the region. As the eastern terminus of the lucrative Santa Fe Trail, Independence was just six miles from the Blue Mills landing on the Missouri River. The trail continued past Santa Fe to the south to reach Chihuahua, Mexico, allowing traders to circumvent the high taxes of naval trade at the port of Veracruz. Samuel C. Owens and others recognized that “traders needed a town where supplies and livestock could be purchased and freight could be transferred to and from St. Louis by river, a town where they might finalize legal transactions and assemble goods for freighting to Mexico, and where they could monitor each other’s business interests” [O’Brien p. 34]. Three factors interfered with the continuing growth of Independence. Their interaction with Mormon immigrants from the east rapidly became disastrous (1827-1833). The Mormons fled across the Missouri River to Liberty in Clay County, where the refugees found less-than-hospitable hosts. The primary school that I attended in Liberty was named for Alexander Doniphan, a lawyer, soldier, and legislator who agreed to represent the Mormons in court. The disputes with Spain and the Mexican-American War of 1846-1848 compromised the value the Santa Fe trail represented. The Bleeding Kansas Border War between 1854 and 1861 had a heavy toll on the region, to say nothing of the American Civil War. Today, Independence has become the fourth largest city in the state rather than the first.
In many respects, Westport was an attempt to swipe Independence’s role as the trail head for Santa Fe. If one could unload steamers even closer to the bend of the Missouri River than at Independence, a couple of days could be cut from the wagon travel time. In 1833, John C. McCoy decided to divide the lands around his trading post into lots for sale. The site, approximately four miles south of Chouteau’s Warehouse, lay along the trail from Independence to the southwest. Growth at Westport was sluggish at first, but then the 1837 Platte Purchase altered the Missouri state line to follow the Missouri River rather than head directly north; previously, this wedge of land had been used to re-home Native Americans from the east, and now they were being removed again.
Gabriel Prudhomme, one of the settlers at Chouteau’s Warehouse, had acquired some premium property at the site including a rocky landing on the riverside. His untimely death in 1831 resulted in a sale of his lands, and the buyers were fourteen investors who bought it to create the “Town of Kansas” (among them was John McCoy). In effect, the Prudhomme estate purchase made it possible to link Chouteau’s Warehouse with Westport. An 1838 survey established a set of lots for the expanded city, but a variety of mistakes led to contested claims. After a powerful flood of the Missouri River in 1844, the first brick buildings in the city were constructed in 1845, with the last of the initial lots selling in 1847. In 1850, the Town of Kansas was finally incorporated. Only three years later, it was renamed the City of Kansas. By contrast, nearly forty years had passed before the name was changed to “Kansas City!”
Since flu season can last until May in the Northern Hemisphere, a person appearing in the emergency department with nonstop coughing and labored breathing could represent influenza or COVID-19. Given that we have now confirmed that more than 100,000 people have a case of COVID-19, it is clear that we need clinical tests to find the people carrying the SARS-CoV-2 virus (you may also see the name “2019-nCoV” used). This blog post is intended to explain the “real time reverse-transcription polymerase chain reaction” used to confirm that SARS-CoV-2 has infected a patient.
As a starting point, I would note that real time RT-PCR is a mainstay in humanity’s battle against coronaviruses. In 2003, a team at University of Hong Kong published an optimized method of this type for recognizing the earlier SARS virus. Since the 2019 SARS-CoV-2 virus is a close relative of SARS-CoV-1, it makes sense that we would adapt the tools from our earlier epidemic to the current one.
How real time RT-PCR works
In my earlier post, I noted that the genome of the SARS-CoV-2 virus is a positive-sense single-stranded RNA. To use a technical term, RNA is twitchy; if a newcomer tries to work with it in the lab, we frequently find that the molecule degrades due to pH changes or RNAse enzymes that chop it up. One of our first moves, then, is to make a DNA molecule that is the complement (opposite strand) of the virus RNA genome. This requires an RNA-dependent DNA polymerase (also called a “reverse transcriptase”), an enzyme used by retroviruses like HIV to manufacture DNA from an RNA template. Making cDNA from the RNA in a sample makes a stable copy for what comes next.
Polymerase Chain Reaction (“PCR”) is a technique that is absolutely indispensable to modern molecular biology. Ideally, each cycle of PCR doubles the number of copies of a targeted piece of DNA. Even if one is starting with a modest number of DNA molecules, a few cycles can boost those numbers considerably. Ten cycles at perfect efficiency, for example, should “amplify” each starting molecule into 1024 copies. One of the protocols created in Germany to detect SARS-CoV-2 allows for up to 45 cycles of PCR, meaning each starting molecule would become 35,184,372,088,832 copies (again, assuming perfect efficiency)! Amplifying with PCR is essential in the clinical test because we need enough copies of the genome to be able to detect them.
The last aspect I want to explain is the first part of the name, “real time.” In the bad old days, researchers would radioactively label probe DNA to determine whether or not it had annealed in a particular spot. If photographic film became dark in that spot after a long exposure, we knew that that our probe DNA annealed. We are much happier today that we can use fluorescent reporter dyes for instant feedback. Ideally, we want a fluorescent system in place that will tell us how many copies of our target DNA are present in the sample so that this is a quantitative assay (Often you will see this written as “qRT-PCR” to reflect that goal). We check fluorescence after every cycle of PCR. When we detect a sure fluorescence signal (one higher than a pre-specified threshold), we write down the cycle number as the “Ct” value for this sample.
It’s all about the primers
Since real time RT-PCR is such an established method for virus screening, one might wonder why many patients in the United States have found it difficult to get themselves tested. The journal Science and the Washington Post have both recently published on the mistakes that prevented the Centers for Disease Control and Prevention from mass-producing a test for use throughout the United States. For the U.S., the usual sequence of events for a new disease test looks like this:
Typically, there are few confirmed viral samples from patients at the outset, which researchers need to validate their tests, and CDC has the capability to grow the virus for this critical quality assurance step. Once the agency has a working test, that goes out to state labs. Then, in a third phase, commercial labs take over and either produce their own tests or scale-up the CDC one.
China developed an qRT-PCR test at a very early stage, publishing their test on January 21, 2020. Germany was also out of the gate early, publishing their test on January 17, 2020 (their approach was adopted by the World Health Organization). The CDC’s own test was made public on January 24, 2020. If you are interested, you can even review the step-by-step directions for conducting the test. I was proud of my alma matter, the University of Washington, for creating their own assay to detect this virus because of the outbreak in the city of Seattle.
These assays all use different primers, the DNA guides that specify which pieces of DNA are amplified in PCR. The primers need to be designed to match parts of the viral genome that are conserved (unchanging among all circulating viruses). The sequence chosen for the primer is also important because it must be very specific to the virus to be detected. If the primers were picked for an area that is common to all coronaviruses, we could determine that one of these viruses were present (SARS-CoV-1, SARS-CoV-2, or MERS-CoV) but not which one is present.
If primers are chosen inconsistently, it is possible that a sample could appear positive on one test (because its viral sequence matched the test 1 primers) while appearing negative on another test (because its viral sequence did not match the test 2 primers). Naturally, we’d like all the tests for COVID-19 to agree perfectly. At present, NCBI Virus shows 108 different virus sequences for SARS-CoV-2. The China National Center for Bioinformation, on the other hand, has released 380 virus genome sequences! Our ability to discern good places and poor places to align our primers is getting better with each new sequence.
Putting the tests to work
From what I’ve written above, it would seem that the CDC was ready to start wide screening for SARS-CoV-2 in late January. Two big barriers, however, stood in the way.
First, when CDC released the test for use in state laboratories on February 5th, several of the laboratories reported getting a positive result on the negative control that was distributed with the test. Naturally, we want to avoid two types of error with any clinical test: we do not want to claim healthy people are sick, and we do not want to claim sick people are healthy. We include negative controls in our COVID-19 tests so that samples known to lack the virus are tested alongside “unknowns.” If we see a positive result for a control known to lack the virus, something is wrong with the test. Multiple states reported that the tests they received from the CDC produced positive results for the negative control. As a result, they were allowed only to forward their samples to CDC for centralized testing.
The second chief problem came from CDC’s guidance on who could be tested for the virus behind COVID-19. Only patients who had recently traveled to Mainland China or who had been exposed to a person known to have been infected by the virus could be tested. As a result, we neglected to test people we later realized were carrying the virus to others in the community. As of this writing, the guidance on testing has been expanded:
Priorities for testing may include: 1) Hospitalized patients who have signs and symptoms compatible with COVID-19 in order to inform decisions related to infection control. 2) Other symptomatic individuals such as, older adults (age ≥ 65 years) and individuals with chronic medical conditions and/or an immunocompromised state that may put them at higher risk for poor outcomes (e.g., diabetes, heart disease, receiving immunosuppressive medications, chronic lung disease, chronic kidney disease). 3) Any persons including healthcare personnel, who within 14 days of symptom onset had close contact with a suspect or laboratory-confirmedCOVID-19 patient, or who have a history of travel from affected geographic areas within 14 days of their symptom onset.
A look at the current map of worldwide COVID-19 cases is haunting. More than 4000 people have died, and 114,000 people have been diagnosed with the disease (and those numbers will be out of date by the time you read this). The most recent situation report from the WHO, however, shows some really good news that I want to highlight (numbers come from report 49):
As the nation where this virus was first observed, China has borne the brunt of COVID-19 disease, with more than 3000 of the deaths taking place there. It may surprise you to learn that China diagnosed only 105 people with the disease in the last 24 hours (45 confirmed, 60 suspected). During that same period, an additional 23 people died of COVID-19. These losses are tragic, but they also represent a huge drop versus what China was facing on Valentine’s Day. This epidemic can be beaten, and the measures China has taken have been effective.
The Republic of Korea has a different governmental system than China, of course, and that made some differences in what policies could be used to limit spread of the disease. Korea opted to make widespread testing its mechanism to ensure that people with the virus spread it no further. They even created “drive-through” testing centers (an idea later adopted at the University of Washington). Their surveillance was able to detect cases as soon as possible, cutting into the hidden transmission of the virus. In Situation Report 49, we see that Korea has diagnosed a total of 7382 cases of COVID-19, with only 248 added in the last 24 hours. They are beating this disease because they are screening for it.
As countries all over the world are detecting the arrival of COVID-19 on their shores or are detecting growing numbers of cases each day, it is worth remembering that public health officials are doing their best to get ahead of this virus. We have many miles left to go, but I imagine that two or three months from now, the initial panic will have given way to determination. We will drive the new infection rate for SARS-CoV-2 to zero!