Learning about Tuberculosis at the Opera (Again)

I had one more tuberculosis-related opera on my list and just had the opportunity to experience it. Again, the disclaimer — I am not a regular opera consumer but am someone who has an interest in consumption. Verdi’s La Traviata which predates La Boheme, is based on a novel and play that recounts the life and demise of a famous courtesan from tuberculosis. Since it was written several decades before La Boheme it is not surprising that tuberculosis is a fatal disease.

One of the elements of this tuberculosis portrayal is that the main character, VIoletta, is a well-accepted, highly sought-after person of interest despite her sickness. Today, tuberculosis is known as a contagious infectious disease and those with pulmonary tuberculosis (who are smear positive and not on therapy) are not the people who should be interacting all that much with the general public until their disease is under control.

Robert Koch discovered Mycobacterium tuberculosis as the cause of tuberculosis in 1882 — decades after La Traviata — dispelling mistaken notions regarding the cause of tuberculosis, including heredity or a disposition/temperament. In La Traviata, there is a line about how a person lives confers susceptibility (which is not entirely untrue) but in the opera it appears to matter-of-factly be more about continual parties and being a courtesan than any moral judgment.

Perhaps the lack of fear of contagion explains why tuberculosis wasn’t stigmatized at that time and it was only with Koch’s discoveries and the acceptance of the germ theory of disease, that tuberculosis exposure was re-conceptualized as something to be avoided. When tuberculosis modern descendant (in terms of widespread infection, targeted demographic, etc) appeared that type of view of disease

The Perfect Predator is the Perfect Lesson in Persistence

I have been a proponent of the concept of using bacteriophages as medical treatment for some time. They have always seemed, to me, to be an elegant precise solution to bacterial infection. Phages, viruses that infect bacteria, avoid the issue of antibiotic resistance and antibiotic side effects. They are safe — every mouthful of water is chock full of them— and ubiquitous and have a fascinating history. I have written about their use and advocated policy changes in order to facilitate their adoption but often this was not compelling. A new book by infectious disease epidemiologist, Steffanie Strathdee and her husband psychologist Thomas Patterson, does, however, provide a compelling case that will not be ignored.

The events detailed in The Perfect Predator: A Scientist’s Race to Save Her Husband From a Deadly Superbug center on Patterson’s acquisition of a life-threatening multi-drug resistant Acinetobacter infection overseas and the Herculean efforts Strathdee expends in order to save his life. The book exquisitely details the daily ups and down of Patterson’s critical illness as he is continually swallowed in the throws of septic shock. Had this happened to anyone other than Patterson and Strathdee, that would be the end of the story but Strathdee excelled at finding a non-traditional cure for what would in 99 out of 100 instances a terminal infection.

Strathdee turned to the forgotten technique of using bacteriophages and, by now, this part of the story has been well publicized. What I particularly gained from reading this book was the diligent efforts of teams to match phages to the exact strain of Acinetobacter, construct cocktails, and work out the logistics of intravenous administration all the while successfully navigating the bureaucratic hurdles needed to use such a product.

Strathdee’s impassioned fight for her values, using cutting edge science and first-rate minds (including her own) to find an elegant solution is a lesson for how the battle against antimicrobial resistance can be won. Pushing through barriers, removing obstacles, following the science, and relentlessly persevering are important emulatable attributes that should be brought to bear on what is arguably the greatest health crisis humans currently face.

By paving this road, Strathdee has become a great benefactor of humankind.

Burden of Genius: Heroes Do Exist

I’ve written about the heroic and pathbreaking work of pioneering Pittsburgh-based transplant surgeon Thomas Starzl before. No amount of praise however can do justice to this benefactor of humankind who developed the technique of liver transplantation. A new documentary, however, is an important homage to the surgeon and scientist whose genius-level breakthroughs changed the world for the better.

The documentary is entitled Burden of Genius and I believe this to be apt as Dr. Starzl was light years ahead of colleagues and could see a solution to what many saw as an insoluble problem. Not surprisingly, like many innovators, Starzl had to waste time battling bureaucracy, rumors, and irrational opposition to ultimately prevail.

The documentary features interviews with Starzl, his colleagues, his family, and his mentees. What shines through every second of the film, is the love of his work that Starzl embodies. He practiced the virtue of productiveness to such a degree that he almost seems to be a fictional hero, but he wasn’t fictional and the insurmountable obstacles he traversed really existed and were surmounted. He is someone to emulate no matter your career.

The film details the ups and down of building a liver transplantation network: the deaths and the failures as well as the stunning final successful result. Pittsburgh and its hospital systems are what they are today because Starzl took the baton from Carnegie, Mellon, and Frick. The same could be said of transplantation as a whole, immunosuppression, and transplant infectious diseases.

I never met Dr. Starzl in person though I had seen him walking around the University of Pittsburgh and UPMC campuses several times. I even heard him lecture once. One of my greatest memories, though, was at even honoring my mentor DA Henderson, the architect of the eradication of smallpox. As DA finished his talk, he approached me and I realized Dr. Starzl was there too. “DA, there’s Dr. Starzl, “ I said as he approached. I was completely in awe to see these two giant benefactors of mankind in the same room interacting with each other.

As a physician watching Burden of Genius, I was completely inspired to work harder, push myself further, and use my mind more fully and for that alone the film is invaluable.

I hope it has a wide audience.

Going to the Opera to Learn About Tuberculosis

Last month, on March 24, it was “World Tuberculosis Day” and it likely came and went without notice. Though tuberculosis is something that often doesn’t make headlines much, it is #1 infectious disease killer of humans. It killed 1.3 million people in 2017—more than flu, HIV, malaria, and measles. It has infected about one-quarter of the world’s population. Though the US tuberculosis burden has fallen to record lows (9105 cases in 2017), it nonetheless remains an important public health threat.

A disease that leaves such a mark on humanity is bound to leave its mark on culture as well. Probably one of the most famous cultural monuments to tuberculosis is the Puccini opera La Boheme, which I finally was able to see earlier this month. To modern audiences, La Boheme is probably more noted for being the inspiration behind Jonathan Larsen’s Rent rather than in its own right.

I am not an opera aficionado by any standard and don’t really know how to evaluate operas, but I am an infectious disease nerd and that’s why I wanted to see La Boheme. La Boheme, just like Rent, is centered around a group of artistic, financially challenged friends one of whom has an advanced case of tuberculosis (Mimi). The plot revolves around the friends daily trials with romance, career, and (not surprisingly) rent.

La Boheme was written in 1896 nearly half a century before streptomycin — the first anti-tuberculosis antibiotic was discovered — and about three decades before the BCG vaccine was developed. At that time, tuberculosis was incurable so it is not surprising how La Boheme ends. Interestingly, during that era, TB was thought by many to be an inspiration to the artist as well as a manifestation of beauty (this was part of the “illness as metaphor” work of Susan Sontag). Today, I don’t think that impression persists as tuberculosis patients are often stigmatized for various reasons and no one is claiming tuberculosis is “romantic.”

Seeing infectious diseases portrayed in great works of art importantly concretizes how impactful they can be and for that reason, I thought La Boheme is an important part of understanding the cascading effects of infectious diseases that spread much farther and deeper than many other medical conditions.

Far Reaching Implications--A Review of Synthetic Biology: Safety, Security, and Promise

Anyone who reads anything regarding biotechnology, often comes across the concept of synthetic biology and its prospect to revolutionize the field and positively impact human life — a sentiment that I share. In essence, synthetic biology is the engineering of biological systems and components, including organisms. CRISPR babies, 3 people children, gene defects edited away, creating life from scratch, and myriad other examples illustrate the power of synthetic biology. Synthetic biology is not just the stuff of engineered organs for transplantation but also a force in such disparate fields ranging from vanilla beans to anti-malarials to tires. Even truffles — the most expensive food — are now the subject of synthetic biology.

Synthetic biology, like all technologies, raises important questions regarding its use, its proliferation, its dissemination, and its overarching implications. This is especially true as it “makes biology easier to engineer” at 10 cents per base pair. To grasp the swirling discussions that surround synthetic biology from both a scientific and policy perspective, a primer can be invaluable in shaping one’s thinking, prompting new questions, spurring new integrations, and concretizing what for many is a nebulous concept.

Fortunately, a book my stellar colleague and friend, Gigi Kwik Gronvall, published in 2016 — which sat on my stack of books to read for way too long — serves as an excellent introduction to the subject that equally appeals both to those with advanced knowledge of the topic and those with a general interest. Synthetic Biology: Safety, Security, and Promise is focused on highlighting the high-level policy issues that relate to technological development and importantly seeks not to curtail this life-enhancing technology, but to ensure it proliferates and its capacity for good is fully realized.

The book is divided into five chapters that address issues from four angles) security, safety, ethics/public engagement, US leadership/competitiveness) plus a chapter on the “New World” ushered in by synthetic biology. Throughout the book Gigi makes a point of warning about the consequences if synthetic biology is not kept relatively free “from the barnacles of bureaucracy” that “have made research harder, slower, and more expensive” — as the legendary Dr. David Franz puts it in the book’s introduction.

Gigi covers some of synthetic biology’s cardinal achievements such as the synthesis of the life-saving anti-malarial artemesinin and the “boot up” of the bacterium Mycoplasma mycoides genomere.

Some important points that are made and merit emphasis include:

• “If the US is not on the leading technical edge of synthetic biology advances, it will be disadvantaged in setting rules and common practice for the governance of the technologies”

• “Losing competitiveness in synthetic biology could also limit specific security applications on the horizon that are essential for national defense”

• “It is important to note that there is no requirement for synthetic biology or other new technical advances in order to misuse biology or biological organisms” (though it is true that synthetic biology makes it possible to make a biological organism from scratch)

• “Cutting and pasting together strings of DNA has been going on for decades in molecular biology and has thus far been proven exceptionally safe”

• “For new technologies, there is a temptation to stifle innovation on the basis of fear of the unknown, but regulatory burdens can be counterproductive to security and safety”

“Every day is a biology news day” is the first sentence of chapter 1 and it is a great way to summarize this book and indeed all of biology. Biology, to me, is endlessly fascinating and represents one of the best examples of human’s success at first understanding themselves and the world around them and then reshaping it to further human life. Gigi’s book helps document that journey and provides a path forward that will allow this flourishing to continue.