Burden of Genius: Heroes Do Exist

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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.

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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

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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.

Read With A Grain of Salt: A Review of Jeremy Brown's Influenza

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It is not surprising to see books being released at the centenary of the 1918 influenza pandemic, arguably the greatest infectious disease threat the human race has ever encountered. I have devoured many books on this event, covering many different facets of what was a global catastrophic biological event like no other in which up to 100 million people perished and cascading effects impacted every aspect of human civilization.

A new book focused on this topic was recently released and, unlike many other books I have read on this topic, was decidedly mixed and at times veered towards a conspiratorial tone. Books on infectious diseases are not immune from conspiratorial speculation but I was surprised it was present in one authored by an NIH physician.

Influenza: The Hundred Year Hunt to Cure the Deadliest Disease in History by Dr. Jeremy Brown is a book that delves in depth into the origins of the pandemic virus and the quest to unlock its secrets. This is the book’s strong suit. Dr. Brown, fittingly begins his book with an anecdote set in Pittsburgh recounting the harrowing experience of a young woman ravaged with influenza who required extra-corporeal support. (This patient, coincidently was taken care of at UPMC and I think I was one of the physicians who initially saw her.) Dr. Brown’s book has many positive attributes that include:

  • A discussion of early treatments of influenza (including blood-letting)

  • An exploration of hypotheses regarding the extraordinary impact of the 1918 virus

  • The resurrection, via science, of the 1918 influenza virus

I found his discussion of the cascading impact of flu on the life insurance and pension industries particularly illuminated as it illustrated how economically important pandemics and severe influenza seasons can be (good for the pension industry bad for life insurance companies).

Brown also explores the differences in how flu is conceptualized in different countries. In the US, there is an aggressive approach to influenza with universal vaccination as a goal and a stress on the complications of flu while in the UK a decidedly different approach is taken. In the UK, cost-effectiveness analysis (necessitated by their socialized, single-payer healthcare system) has found that the optimal targets for vaccination are children, the elderly, and those at risk for complications — the cost-effectiveness analysis is restricted to direct healthcare costs and does not account for absenteeism, lost income, and other costs. Interestingly, Brown also draws attention to the British “keep calm and carry on” attitude towards influenza which is thought of as just “a bit of a nuisance” with no mention of the severe complications such as death that are highlighted on the CDC website but not the NHS.

Where I depart with Dr. Brown is on his position on flu antivirals and flu testing. With respect to flu testing, Dr. Brown, who works as an emergency medicine physician, is of the mind that it does not change treatment and the epidemiological value gained by specifically diagnosing cases does not justify the expense and the effort of reporting cases to public health authorities. Dr. Brown tends to treat patients with over-the-counter medications and the test does not change his treatment. However, multiple studies have shown that many flu patients are inappropriately prescribed antibacterial treatments and flu testing enhances antibiotic stewardship. Moreover, some hospitals collect flu data and use it to trigger specific actions from infection control and hospital administration when the season is in effect. This anathema to testing also likely derives from Dr. Brown’s position on antiviral therapy for influenza.

There is a group of individuals, of which I believe Dr. Brown is a part, that doubt the efficacy of antiviral medications to make meaningful impacts on influenza. Drawing on the studies in healthy individuals with flu which revealed a modest decrement in symptoms, this group eschews the use of flu in high risk patients for whom the drug is considered life-saving based on observational data. Indeed, such a position of liberal use of antivirals in those at high risk for complications is embraced by the Infectious Disease Society of America (IDSA) guidelines. Dr. Brown also engages in speculation regarding the pandemic stockpiling of Tamiflu and the lobbying efforts of Roche, tying them to a suicide of a wealthy lobbyist who worked to raise awareness of the threat of avian influenza.

Overall, I recommend this book to those interested in influenza and the 1918 pandemic. The book is well-written and easily accessible however I do believe non-medical readers should approach the book with an active mind but could still have time grappling with the arguments made regarding antiviral therapy and diagnostic testing. For those with more knowledge of influenza, it is a good read that will challenge you to dissect arguments while learning more about flu.


Guatemalan Migrant Child Flu Death Illustrates Larger Deficiency in How Influenza is Managed

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The tragic and likely avoidable death of a recent death of a Guatemalan child migrant in US Custody from influenza (type B) illustrates many deficiencies of how physicians and other providers mismanage influenza. In addition to the unique circumstances of the child’s detention that are being reviewed, there are important aspects of this case that merit scrutiny from a medical perspective.

  1. The common cold does not ordinarily cause 103 degree fevers. The boy was reportedly diagnosed with the common cold after his medical visit yet exhibited fevers of 103F. While it is true that some benign viral infections in children can cause high fevers, I don’t think it is the usual course for a common cold caused by rhinovirus. In most circumstances a search for another etiology (including pneumonia with a simple chest x-ray), especially in someone who is a traveler and is being housed with many other travelers would be pursued. Additionally, there are ways to confirm the common cold through respiratory viral panels that are widely available, use sensitive molecular technology, and are rapid. It appears the patient was tested for Group A Streptococcal infection (“strep throat”) alone.

  2. Antibiotics are not needed for the common cold. If one diagnoses the common cold, antibiotics are not warranted and are wrong to prescribe. The common cold is caused by a host of viruses and no antibiotic is indicated for their treatment. In fact, prescribing an antibiotic is incorrect and exposes the patient to unnecessary side effects and fosters the development of antibiotic resistance in the patient. Additionally, an antibiotic prescription may give one the false idea that they should wait out the illness waiting for the antibiotic to “kick in” when, for a viral illness, it never will. If the provider believed the patient to have the common cold — which was not confirmed — what justified the use of an antibiotic?

  3. Flu (and other viral) testing and antiviral prescribing are underutilized. While it is true that clinicians are good at spotting influenza clinically in many cases and treated appropriately, it clearly wasn’t the case here. There are myriad flu tests available however it appears none were used in this case (not even the poorly sensitive rapid tests which are not recommended for use in the latest Infectious Diseases Society of America guidelines). Testing for flu helps establish the diagnosis and is often a prompt to prescribe antiviral medications as well as to refrain from prescribing antibiotics.

It is clear that this child’s experience was not usual — he may have been dehydrated, malnourished, not vaccinated against influenza, and suffering from other conditions — but his death really should prompt scrutiny of how the medical community interfaces with influenza in all settings. We will face future severe flu seasons and future pandemics. It is only by becoming adept at dealing with seasonal influenza that any resiliency to influenza pandemics will develop. As this case and others in migrant and non-migrant populations will illustrate in the upcoming season which has already accumulated 11 pediatric deaths, clinical management of influenza needs to be optimized.