Francesca Tomasi received her B.A. from the University of Chicago and is now a microbiologist.
I handle tuberculosis almost every day. But I'm not a doctor. Before March 2016, I had never met a tuberculosis patient. I am a researcher, and multiple times a week I don a slew of personal protective equipment and shuffle loudly (the suits are made of a papery material that would instantly lose you any hide-and-seek game) into a Biosafety Level 3 laboratory. In the negative pressure room, I pick, pipette, and pour samples of Mycobacterium tuberculosis to the soundtrack of loudly humming machines and incubators that occasionally beep to let me know they're still working.
Mycobacterium tuberculosis is a Biosafety Level 3 pathogen for a reason. There are 4 Biosafety Levels, conveniently named 1 through 4 in ascending order of the deadliness and virulence they are equipped to house. The causative agent of tuberculosis is just shy of the crown of a Level 4 pathogen simply because we have drugs to treat it and we know how it spreads. Nonetheless, it goes without saying that anyone knowingly handling TB does so in a high-security, tightly-regulated, scrupulously-maintained, isolated laboratory. We go through an abundance of training, learning the do's and don't's of Biosafety Level 3 work, before we are even allowed in the lab. It's all for a good reason: no one wants TB. TB kills. This cunning microbe has been around since the dawn of humanity, yet we still tip toe around it the way we do with anthrax, HIV, and novel flu strains.
I started working with TB a year ago, and since then I have grown numb to the stifling aspects of medical respirators, save the time when I sneezed heartily into my mask thirty minutes into a three-hour assay. I will never become sophomoric about safety, though. Most of America might be blissfully unaware of the dangers and startling ubiquity of Mycobacterium tuberculosis, but I am fully aware of the risks, symptoms, and prognosis of infection. It's not a job for a hypochondriac, but then again it kind of is.
As I said, before March 2016 I had never met a tuberculosis patient. And - unless it was unknowingly - I had never met a tuberculosis survivor. So when I woke up at the crack of dawn on March 24th to begin a long day of advocacy for increased tuberculosis research funding, I was a little nervous. I had read about this event on Capitol Hill on the Internet and signed up on a whim.
High-containment labs are meticulously well-kept. Our lab manager regularly samples the area for any containment issues, safety breaches, or equipment malfunctions. We know exactly how much TB we are working with and we always have a bag of a thick, bactericidal fluid propped up next to us in the event of a spill. But what about high-containment people? Of course, the United States public health system would never allow a patient with an active TB infection to walk around in public; patients are quarantined until they test sputum negative for the bacteria multiple times in a row. All the TB survivors I was going to meet that day had been invited by local advocacy groups to speak to their state representatives, so clearly they weren't sick. But in the back of my head I couldn't help but wonder What if someone coughs?
In case you stop reading here, I want to stress right now how stupid and paranoid I was being. Not only was I being stupid and paranoid, I was also propagating the exact mindset I created this website to abate: stigmatization of survivors of an infectious disease. There is never a reason to stigmatize an infectious disease. Pathogens don't respect boundaries; they don't pick and choose who they're going to infect. The people I met were incredible. They were beautiful, strong, brave people. They were women who survived a pregnancy wrought with tuberculosis and endured months of unrelenting chemotherapy and fear that their child would not make it. They were musicians who had played numerous jazz concerts before being diagnosed with a disease that was ravaging their lungs. They were recently-retired artists whose marriage succumbed to the devastating effects of such a draining illness. They were investment bankers, athletes, accountants, mothers, fathers, brothers, and sisters.
They all survived history's deadliest plague, and they all had every right to live a normal, stigma-free life. They had stories to tell in undying efforts to prevent other people from going through what they had to go through. They were all so much more than the disease that had stolen years from their lives, their marriage, their career. Listening to their stories, admiration washed over apprehension. I vowed never to look at a patient differently again. I drank in their words, eager to channel their perseverance in my own laboratory crusade against tuberculosis.
I have loved science since I can remember. As a child I would tinker with microscopes, play with chemistry sets, and collect fossils. Growing up, I saw science everywhere: the miracle of radios, birds defying gravity, viruses that made us sick, roller coasters that never broke, computers that let us do basically anything. But as I made my way in and out of college, as I became more involved with science as an institution rather than a hobby, the more I noticed that we work in an ivory tower. This tower is home to inquiry and ingenuity, innovation and imagination. Some of the most intelligent people I have ever met are scientists, and the papers I read every day opened doors to increasingly brilliant and fascinating discoveries.
But it seemed to stop there. You would spend months or years on a project, obsessively making sure every assay was properly performed, every experiment had a control, and your data was reproducible. You would then tirelessly write a paper encompassing your methods, findings, and conclusions. You would submit your paper to academic journals and, if you were lucky, you would get your work published. Then it was over. Time for the next project.
That's how I felt as I went into my TB research job. I was going to work here for a couple of years, try to finish some projects, get them published, and get into a good graduate school. However, World TB Day changed everything about my mindset. Meeting living manifestations of the bug I was studying instilled in me a sense of urgency for my research that I had never felt before. One tuberculosis survivor even told me, "I better turn on the TV one day and hear you guys made a vaccine against this thing." Meeting tuberculosis survivors and hearing their poignant stories showed me exactly what science had accomplished (hey, they had all successfully been cured thanks to the existing antibiotics to treat TB) and what it still had to do. These people had been cured, but they had suffered terrible side effects as a result of the potency of the drugs they took. It took them at least a year of pills and injections to be cured. Rapid diagnostics were nowhere to be found when they first became ill: on average, it took these survivors about four months to be diagnosed with tuberculosis in the first place. We have not seen a "newer, better" TB drug in decades. We don't have an efficacious vaccine against it. Oh, and the medical community has become so complacent with TB's status as a Third World Disease that tuberculosis has been ignored in many developed countries. Tuberculosis is also re-emerging globally as a drug resistant disease, and our current repertoire of drugs no longer works for every patient. To this vein, tuberculosis rates are plateauing in America instead of continuing on the downward trend we expect them to be on in a country with robust public health infrastructure and at the forefront of biomedical research.
Needless to say, being an active participant on World TB Day ripped me out of my microscopic world, lifted my chin, and forced me to look straight ahead at the macroscopic world. This isn't a job for an ivory tower. This is a job for the human-scientist. A human-scientist doesn't isolate themselves from the overarching goals of their research. A human-scientist leaves their lab and enters the world, if not only to see how things are going. A great human-scientist is a superhero: someone with the acumen to translate problems into experiments, and someone who identifies these problems in the first place.
March 24th, the day I was on Capitol Hill, marks the anniversary of Robert Koch’s discovery in 1882 of the bacteria that cause TB, Mycobacterium tuberculosis. Looking at an electron micrograph picture of the microbe (below), you would never think such a simple-looking, beautiful pipe cleaner-like rod has killed more people in human history than any other bug. I was on Capitol Hill to supplement survivors' stories with my own experience as a researcher, to explain why such an ancient pathogen was still a public health threat.
I had a lot to say the day I became a human-scientist.
The truth is that the TB bacterium is as dangerous as it is complex. In 1998, scientists whole-genome sequenced it. Its genome consists of over 4.4 million base pairs, the building blocks of DNA. This equates to about 4,000 genes dedicated to producing the world’s most dangerous microbe. Bacterial genetics is the study of the genetic components and mechanisms of these organisms, and researchers have spent the last two decades deciphering the complex genome of M. tuberculosis. An understanding of which genes are essential for TB’s survivability provides essential insights for drug-makers: find or design a compound that inhibits an essential gene product (with the giant caveat of not simultaneously damaging human cells), and you have yourself an antibiotic.
The problem with TB, a product of its large genome, is its incredibly complex cell wall. The cell wall is a structure composed of many different molecules, usually fats and sugars, that serves as bacteria’s barrier from the environment. Most bacteria are classified as “gram negative” or “gram positive” according to the color they stain in a Gram test. In a Gram test, bacteria are stained with a violet dye, rinsed, and counter-stained with a red dye. In one type of cell wall, rinsing does not successfully remove the first dye and the bacteria appear purple. In a different, thinner cell wall, rinsing decolorizes the bacteria and the second stain is visible, creating pink colonies. Gram negative bacteria stain pink because their cell walls are not as thick as Gram positive bacteria, which stain purple. Mycobacterium tuberculosis is different from both Gram positive and Gram negative bacteria, and cannot be reliably colored in this test. This is due to its incredibly thick, complicated cell wall. This cell wall is thicker, waxier, and rich in substances known as mycolic acids, which are large fatty materials that naturally make it very difficult for unwanted molecules, such as antibiotics, to penetrate the cell wall. There’s your first physical barrier against TB treatment.
The physical barrier also serves as tuberculosis’s Achilles heel. Because it is so complex and essential to the survivability of the bacterium in the environment, it offers several prospective drug targets. In fact, this is a huge area of TB research, which also looks at other bacterial metabolites as potential drug targets. M. tuberculosis is very slow growing due to its complexity: whereas most bacteria, as you have probably heard, can replicate every 20 minutes to an hour, TB takes the better part of a day to replicate itself. Such slow growth hinders both research and treatment. In the former, experimental assays need to be carefully planned out and executed because it can take anywhere from 2 to 6 weeks to obtain results. In the latter, treatment has to last for an exceptionally long time in order to make sure every lurking microbe has been killed, removing the possibility of relapse a few months later.
Most of the TB survivors at the advocacy event had no idea where they caught the bug. They had never traveled to a TB-endemic place, or been coughed on (that they knew of) by someone who was visibly ill. Tuberculosis is not scattered all over the place like dust, suspended in midair for unlucky passersby to inhale as they go about their daily business in the United States, but people are infected, and people spread the disease. About one third of the global population - over 2 billion people - is estimated to harbor a latent form of the bacterium. Latent TB is not contagious and does not make people ill. Latent TB means one’s immune system is keeping the bug in check. However, any immunosuppressing or stressful event – a new medication, a major life change, a pregnancy – can lower the body's defensive walls and let TB run free in the body.
The stories I heard had happy endings, but their tellers had scars. These scars came in the form of partially-destroyed lungs acting as constant reminders that any future lung infection would probably prevail, and that long runs or strenuous exercise would probably be nearly impossible. They came in the form of guilt, the gnawing pain that comes with the question How many people did I infect before I was diagnosed with active tuberculosis? They came in the form of ruined relationships, worry for loved ones, and job loss.
It goes without saying that tuberculosis is a devastating illness both physically and mentally. It has been around as long as humans have, and over time it has cunningly evaded eradication. Rifampicin and other “miracle drugs” discovered in the mid-20th century gave us the chance to end TB, but improper treatment regimens led to drug resistance and re-emergence of the disease worldwide. After a massive and successful effort by physicians and epidemiologists to put the epidemic under control in developed nations, a wave of complacency with the disease washed over these nations. Many doctors were no longer trained to “think TB” when the telltale signs appeared in local patients with no travel history.
Right now, most cases of TB can be cured, yet many aren’t; in other countries, few stories have happy endings. Millions of children have been orphaned by the disease, especially where parents were co-infected with HIV and TB. Four thousand people still die every day from tuberculosis. The WHO estimates that hundreds of thousands of cases go unnoticed every year, which only adds fuel to the epidemic. New drugs have not been developed for the most part since World War II, and no truly efficacious vaccine exists. TB research is expensive, with the added cost of biosafety and training for anybody who handles the pathogen in a lab setting. We are working on it though, and we need to continue working on it until robust results emerge. Tuberculosis has a long and winding past, but in a world where new medical discoveries are made almost every day, where transnational organizations work together regularly to fight the global burden of disease, in a world where interdisciplinary research is no longer the exception but the rule, human-scientists are on the rise and we are ready to cut TB’s future short.