“Tuberculosis is still a thing? Didn’t we cure that already?”
If you are studying tuberculosis (TB) for your graduate/postdoc career in the United States, you’ve very likely heard sentiments like this before. For me, these questions initiate a spiel of statistics that I can recite in my sleep by now:
“Actually, TB is still a big problem globally. One third of the world is infected with Mycobacterium tuberculosis (Mtb), the bacteria that causes the disease. And in 2015, 10.4 million people fell ill with TB, and 1.8 million peopled died from TB. And while yes, there are antibiotics that work against Mtb, many places don’t have the health infrastructure to administer them properly, and therefore resistant strains of bacteria are growing more prevalent.”
Today, March 24, marks World TB Day, a day in which I am at liberty to share that spiel without being prompted. The official purpose, however, is to mark the day in 1882 when Robert Koch (arguably microbiology’s GOAT) announced his work identifying Mtb as the causative agent of TB at a meeting of the Berlin Physiological Society.
I could wax poetic about Robert Koch (yet also bemoan his failure to credit Angelina Fanny Hesse with the suggestion to use agar to grow bacteria) for an entire blog post. But if you’re one of our regular readers, you’re here because you like to learn about issues impacting ECRs, not get a history lesson. And so this year, I will honor World TB Day by sharing my take on the field of TB through the lens of an ECR, specifically by detailing my experience at the Keystone Symposium on tuberculosis (“New Developments in Our Basic Understanding of Tuberculosis”). It seems fitting to share what I learned at a conference on this day, given that it marks not the print publication of Koch’s work but the day he shared it at a conference.
What is a Keystone conference?
It is likely that some of our readers have been to Keystone conferences themselves, but to get everybody on the same page, Keystone Symposia on Molecular and Cellular Biology is a non-profit organization which organizes scientific conferences covering a wide range of topics. And they really do come in all flavors; just in these first few months of 2017, there have been 35 Keystone conferences (counting a few ‘joint’ conferences singly) on everything from bile acid receptors to mitochondria communication. The conference on tuberculosis which I attended was on January 14-18 in Vancouver, British Columbia. This was my first conference of this scale, and also my first which brought together so many different types of tuberculosis researchers. For the full list of speakers and their talk titles, refer to the publicly available meeting program. Rather than give a recap of each talk, I’ll be sharing some key observations which I hope will prove useful for other ECRs in the field of TB.
Top scientists to watch
Full disclosure, I am most inspired by microbiology, and I’m acutely aware that my picks of who to watch are biased towards this field. In no particular order, here are the speakers who best captured my attention and whose work inspired me:
- Carolyn Bertozzi: Dr. Bertozzi spoke on the first day of the conference about work recently accepted by the Journal of the American Chemical Society. I felt Bertozzi explained complicated chemistry to the audience really well, utilizing some great analogies too. She also has an active Twitter!
- Clare Smith: With a speaking style befitting a TED talk, Clare was one of the most engaging of all the speakers. She was also one of the youngest of the long talks, and therefore inspiring as a role model for young, female scientists like myself (and it turns out she is on Twitter too). As for her actual work, she shared recent findings from her postdoc in the Sassetti lab at UMass using the Collaborative Cross mouse model, which I must admit I’d never heard of prior to the meeting. Collaborative Cross mice created by the Jackson Lab are the result of generations of breeding wild mice of three genuses with the most common lab lines. The genetics are carefully tracked, and the result is diverse mice with traceable genetic lineages. This gives scientists the opportunity to study a population, rather than just one type of mouse, which is more representative of a human population.
- Other speakers who stood out were: Thomas Scriba, Veronique Dartois and Mark Cronan.
Sarah Groft, a fellow ECR from Case Western whom I met at the conference, recommended Andrea Cooper as her favorite speaker. Dr. Cooper studies the humoral response in Mtb infection, which continues to be second-class subject matter in the TB community relative to cell-mediated immunity. Sarah acknowledged via an email interview that she was biased to like Dr. Cooper because her own research focuses on antibody glycosylation in the Mtb immune response.
But also that, “It was interesting to hear her defend her research when many of the members of the audience fought back against the idea that antibodies may play a role in the immune response to Mtb infection.”
I agree that witnessing the back-and-forth between the PI’s in the room who had differing opinions about humoral immunity and other topics was fascinating. ECRs are not always privy to debates between faculty—the opportunity to witness faculty standing up for their work was really special.
Emergent Themes and Remaining Challenges
There were a few clear common threads that stood out at the close of the conference, and I also discussed with Sarah what she valued most from the conference. From her experience and my own, I’d give the following as the take-home points about the future of the TB field:
- Diversity: Diversity of antigens used for a vaccine, diversity of an infected population, diversity in how hosts respond to treatments…there are many ways in which diversity comes into play in the TB field. I came away from the conference with a renewed appreciation for considering populations rather than individuals. It was clear that if we are ever to tackle TB, we need to consider many diverse angles to solve such a complex problem.
- Mtb is more than just its antigens: A lot of the T cell immunity talks focused on specific antigens, and I think the moral of the story was that we need to think more broadly than just individual antigens in the search for a TB vaccine. In line with the message about diversity, it seems that combinations of antigens will likely be the best way to get closer to a vaccine. Further, while there was significant push back to the idea that humoral immunity has a role to play, from an ECR perspective it seems strange to disregard an entire arm of the field as a waste of time. Aren’t we always taught not to let dogma cloud our decision-making? While there was only one talk about humoral immunity, there were many great posters on the topic, a highlight being Lenette Lu’s.
- Mice and men: Multiple times, issues where a result witnessed in mice was not reproduced in humans was mentioned. While it is hard to ever imagine the field moving entirely away from mice as a model system, there were good arguments made for obtaining clinical samples whenever possible, and for tools such as the Collaborative Cross mice in attempt to increase the chances that lab findings will transfer to advancements for human patients. A message for young scientists would be to jump on opportunities to utilize clinical samples if you can and use these to strengthen your research.
- Almost more important than a vaccine is better diagnosis: It was clear that a good Mtb vaccine remains many years in the future. But perhaps more attainable is quicker and more reliable diagnostics, which could then get patients on a regimen of antibiotics sooner. “Finding better ways to diagnose TB and determine the differences between latent and active patients–I think these will be two of the fields with the most advancement over the next few years,” said Groft.
Lastly, my biggest lessons from the conference were perhaps not TB facts, but tricks for being a better conference attendee. Read the schedule ahead of time so you have an idea of which talks and posters you don’t want to miss. Check out their papers too if you can. If the poster sessions are in the evening (as they were for this), sneak in some down-time and coffee in the afternoon to make sure you’ll have energy. The poster sessions are an ECR’s best chance to make contacts and pick up on techniques you might want to try yourself. Also be sure to chat with labmates who travel with you or friends you make at the conference to see which talks they liked best and why—this gives you a chance to ask questions and learn from those around you. Above all, have fun immersing yourself in a topic you are passionate about for a few days! You never know when you’ll witness something on par with Robert Koch announcing his discovery at that meeting of the Berlin Physiology Society 135 years ago.
Visit the PLOS Tuberculosis Channel for more
PLOS launched the Tuberculosis Channel on #WorldTBDay 2017. The TB Channel is a hub for the microbiologists, clinicians, public health professionals the make up this interdisciplinary research community to read the latest open access findings that advance the TB research field, and moving that much closer to a better diagnostic model (and maybe someday even a cure).
Featured Image: Mycobacterium tuberculosis by Janice Haney Carr, Dr. Ray Butler, USCDCP, public domain CC0 license.
WHO Global TB Report 2016 infographic, http://www.who.int/tb/global-tb-report-infographic.pdf?ua=1
Centers for Disease Control and Prevention, World TB Day 2017, Division of Tuberculosis Elimination, https://www.cdc.gov/tb/worldtbday/.
Blevins, S.M. & Bronze, M.S., 2010. Robert Koch and the “golden age” of bacteriology. International Journal of Infectious Diseases, 14(9), pp.744–751. http://www.sciencedirect.com/science/article/pii/S1201971210023143
The Etiology of Tuberculosis, Robert Koch, March 24, 1882, from a meeting of the Berlin Physiology Society (in German) http://edoc.rki.de/documents/rk/508-428-445/PDF/428-445.pdf
Popular Science, The Forgotten Woman Who Made Microbiology Possible, July 14, 2014. http://www.popsci.com/blog-network/ladybits/forgotten-woman-who-made-microbiology-possible
Keystone Symposia Mission Statement http://www.keystonesymposia.org/index.cfm?e=Web.MissionStatement
Carolyn R. Bertozzi, Bertozzi Research Lab. http://web.stanford.edu/group/bertozzilab/bio.htm
Rodriguez-Rivera, F.P. et al., 2017. Visualization of mycobacterial membrane dynamics in live cells. Journal of the American Chemical Society, p.jacs.6b12541. Available at: http://pubs.acs.org/doi/abs/10.1021/jacs.6b12541.
Sassetti Lab, University of Massachusetts Medical School, Current Lab Members. http://www.umassmed.edu/sassettilab/people/lab-members/
Collaborative Cross, UNC Computational Genetics, http://compgen.unc.edu/wp/?page_id=99
Thomas J Scriba, Researchgate profile https://www.researchgate.net/profile/Thomas_Scriba.
Veronique Dartois, The Public Health Research Institute, Rutgers NJMS http://www.phri.org/research/res_pidartois.asp
Mark Cronan, Tobin Lab Members, Duke Molecular Genetics and Microbiology https://mgm.duke.edu/faculty-and-research/primary-faculty/david-tobin-phd/david-tobin-phd-lab-members/mark-cronan-phd/
Professor Andrea Cooper, University of Leicester http://www2.le.ac.uk/departments/iii/people/prof-andrea-cooper/professor-andrea-cooper
Lu, L.L. et al., 2016. A Functional Role for Antibodies in Tuberculosis. Cell, 167(2), p.433–443.e14. Available at: http://dx.doi.org/10.1016/j.cell.2016.08.072