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.

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

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

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.

A Tour de Force Defense of Vaccines and Science: A Review of Peter Hotez's Vaccines Didn't Cause Rachel's Autism

Peter Hotez is a rarity in the field of infectious disease. He is, at once, a brilliant vaccine scientist, a science diplomat to the world, a media expert, and an intransigent defender of the prowess of vaccines. I have had the pleasure to interact with Dr. Hotez several times and am always energized by his enthusiasm and passion for this field.

What many people might not know about Dr. Hotez is that he has a daughter with autism which is very significant given that much of the opposition to vaccines is driven by an erroneous debunked claim linking vaccines, thimerosal and whatever has anything to do with vaccines to this condition.

To combat this campaign of misinformation by providing an evidence-based defense of vaccines, along with an extensive discussion of cutting-edge theories and recent data about autism, Dr. Hotez wrote an excellent book. Vaccines Didn’t Cause Rachel’s Autism: My Journey as a Vaccine Scientist, Pediatrician, and Autism Dad, is to me, a tour de force in the field. I have read many book on vaccines and vaccine policies and this one stands out among all of them. Perhaps it is the way Dr. Hotez seamlessly weaves in his and his family’s experiences with Rachel’s autism. He covers the diagnosis, the daily trials and tribulations, the frustrations, and the successes.

Over 12 chapters, Dr. Hotez expertly addresses each vaccine “controversy” (“whack-a-mole”) and illustrates with data and scientific reasoning why such controversies are manufactured and, in my view, essentially arbitrary. He discusses the celebrity culture that abets the anti-vaccine movement as well as the history of the anti-vaccine movement in the US.

Vaccine programs such as GAVI are also detailed with an emphasis on how vaccination in developing countries are a crucial need and how vaccines against neglected tropical diseases are a major unmet need.

There are so many critical insights in this book that is hard to list the highlights. One aspect I took special interest in is Dr. Hotez’s interactions with the media, as this is something I do a lot of as well. Dr. Hotez hypothesizes that some of the misinformation is facilitated by the fact that scientists and physicians do not engage with the general public. as he notes:

“In a survey of 3,748 scientists, only about one-half have ever spoken with a reporter or science journalist about their research, while only 47 percent ever use social media to discuss their science. Only 24 percent have ever blogged about their science and research”

It can be no surprise then that“an overwhelming majority—81 percent—of Americans could not name a living scientist.”

Dr. Hotez also recognizes, as I came to during Ebola in 2014 that

“An added challenge is that public engagement is not usually considered a vital activity for a professor at an academic health center or university. These institutions depend on their faculty to generate revenue through clinical billing or research grants, and such public activities do not generally produce funds. Yet for someone like myself, committed to public engagement or aspiring to become a public intellectual, I have found that writing scientific papers and grant applications exclusively is seldom sufficient to persuade government leaders and policymakers to address a particular group of diseases or an approach to disease treatment and prevention”

I can’t recommend this book enough and hope it has a wide audience of physicians, parents, students, and policy makers. That the heroic Dr. Hotez is the subject of vicious primitive personal attacks is a disgusting fact he should not have to deal with and hopefully this book will help others realize what an asset he is.

Why Did the Chicken Cross the Road? To Get Antibiotics : A Review of Big Chicken

One of the most pressing aspect of the antibiotic resistance crisis is the role of antibiotics in agriculture and the link with human infections. This is an aspect of the problem that has received mixed treatment in the past. It was clear that agricultural use of antibiotics was a problem but its impact on human infections was debated, not well known, and not conclusive though all doctors probably could recite the statistic that 80% of antibiotics sold in the US were for used in animals. Many people, myself included, focused heavily on the superbugs stalking our hospitals and ICU and thought almost exclusively about infection control and human antibiotic stewardship.

However, with the publication of Big Chicken: The Incredible Story of How Antibiotics Created Modern Agriculture and Changed the Way the World Eats, I suspect things will change. This book written by, in my opinion, the premier science journalist, Maryn McKenna, is something extraordinary. I read books in this genre continually and I can saw that McKenna’s ability to tell a compelling non-fiction story while weaving together history, politics, science, and medicine in a manner that teaches and leaves the reader completely captivated is unrivalled.

Big Chicken, which published in 2017, is much more than a book on unraveling antibiotic use in chickens, who are fed “routine doses of antibiotics on almost every day of their lives.” It is nothing short than a history of the chicken industry in the US — which breeds “for everything but flavor: for abundance, for consistency, for speed” — and it is only by understanding antibiotic use in that context that one can really grasp the issue. This is the book’s chief value.

The book teems with so much good information that it is impossible to capture in a short blog post. Some highlights include:

• How antibiotics facilitated the transformation of grain into muscle making an “active backyard bird into a fast-growing, slow-moving, docile block of protein”. Slaughter weights of chickens have doubled in the past 70 years and can be achieved in half the time due largely to the use of growth promoting antibiotics, which allowed chickens to become more than just egg-layers to most farmers.

• The story of the McNugget

• The use of antibiotic-laced harpoons to shoot whales!

• The questionable role of a Mississippi Democrat congressman

• The change in culture that sparked companies like Chick-fil-A and Perdue to revaluate antibiotic use

The book also has great anecdotes of disease outbreak investigations — one featuring a young Mike Osterholm — and scientific studies that increasingly linked antibiotic use in animals to huma infections. The book also discusses how policy evolved with respect to this issue.

For anyone interested in a great story that traces the roots of a major scientific/medical problem, I highly recommend this book. For those who work in infectious disease, it is required reading (as are all of Maryn McKenna’s books).