Plague, Magnet Cities, and the Ottoman Empire: A Review of Plague and Empire in the Early Modern Mediterranean World


One of the most fascinating and impactful infectious disease outbreaks in history is the Black Death. This globally catastrophic event swept over much of the inhabited world in the medieval period when humans entered a cycle of infection between rodents, fleas, and the Yersinia pestis bacterium. There have been many many books written about this topic, some of which I have read. The latest to pop up on my list is very different than many of the others I have read because it is a truly scholarly effort. Plague and Empire in the Early Modern Mediterranean World: The Ottoman Experience 1347-1600 by Rutgers history professor Nukhet Varlik is an exhaustively researched, yet easily readable, treatment of not only how plague impacted the Ottoman Empire but, interestingly, how the Ottoman Empire impacted plague.

The book is divided into three parts and it covers three distinct phases of the plague expertly interweaving the narrative of disease with the workings of the bureaucratic regime that increasingly began to characterize the Ottoman Empire. Varlik shows how the trajectories of a bacterium and an Empire became intertwined. Starting with the nascent empire, Varlik shows how the increasing "constellation of connections" this empire developed -- east/west, north/south -- fostered new vehicles for plague to entire the Empire and to spread throughout and outside of it.

As she writes, "Consolidating the intersecting trade networks connecting the Balkans, Caucasus and Central Asia, Asia Minor, the Arabian Peninsula, Persia, North Africa, and the eastern Mediterranean provided a new set of connections over which plague could spread extensively both within the Ottoman domains and beyond."

A few interesting aspects of the book include:

  • An explanation of the "capital effect" of migration to a major city such as Istanbul, which she labels a "magnet"
  • The fact that not having enough fleas or lice on one's body was considered abnormal during this time period (having none could mistake one for being a leper)
  • The first plague outbreaks spread from Europe to the Empire
  • Once Cairo was incorporated into the empire both a east-west and north-south axis of plague spread became entrenched and plague became more endemic in the Empire
  • Murders could go unnoticed if thought to be from plague

The book's value also lies in how it captures the medicalization of plague and how it moved from being the "decree of heaven" to something that, though the cause was not known, was natural and how reliance shifted from religious to secular authorities. The rise of public health measures in the Empire also developed in response to the plague.

Today plague is largely a forgotten disease in most of the Western World -- indeed people have forgotten that the Western US is home to plague and each time an animal or human case is reported, the media takes notice.

Plague is not the threat it was in the 1300s because humans tamed it through the use of their minds.By discovering its flea vector, describing its various forms (bubonic, septicemic, and pneumonic), and developing effective antibiotic therapies plague was defanged and naturally occurring plague can really never threaten the human race (a bioterrorist attack is whole different matter). However, it is important to be able to recognize what an infectious disease could do under the right circumstances and how networks of trade and commerce facilitate the passage of good and microbes and for this, Plague and Modern Empire is an excellent resource. 

Apres Le Deluge: Infectious Disease Risks and Hurricane Harvey


While the pressing issues regarding Hurricane Harvey's onslaught are responding to the acute needs of those in need of rescue from the peril of flood waters, the coming days and the recovery period will increasingly be characterized by new health-related problems. Among those will be threat of infectious diseases exacerbated by infrastructure failures.

Infrastructure provides clean water for the activities of daily living such as drinking, cooking, and bathing. Infrastructure also separates sewage from living spaces. When infrastructure fails, the chances of contamination by high levels of infectious agents increases tremendously.

Infrastructure has withstood Harvey so far. In the coming days, though, it should be anticipated that more cases of gastrointestinal infections from bacterial, viral, and parasitic causes will increase as people are increasingly exposed to these agents via water. Disruption in the water system need not be complete for exposure to occur as people wade in and are immersed in the water. It will be important that when these cases of GI infection accrue, patients receive appropriate treatment (e.g., hydration) and are prevented from further spreading the illness -- a difficult prospect in a flood-ravaged locale with alternate housing facilities. Leptospirosis from exposure to rat urine and severe Vibrio vulnificus infections are also rare -- but serious -- infections that might occur.

Huddling of people in alternate housing may also facilitate the spread of respiratory viruses and pathogens as people increasingly are kept in close quarters. Hand hygiene will be essential.

Tetanus is also a minor risk as people who are insufficiently immunized may sustain puncture wounds that become infected with the tetanus bacterium -- which is ubiquitous in the environment. Other bacterial infections can occur in this way, as lacerations and abrasions become portals of entry.

Standing water will also be a major concern given the threat of mosquito-borne illnesses in Texas. Standing water serves as breeding sites for mosquitoes and after what has happened in Texas, standing water will likely persist for some time in debris. Zika, chikungunya, dengue, and West Nile all have been locally spread in Texas and would be expected to have enhanced transmission in the weeks after this event.

Much of the decrement in infectious disease in the world today is due to modern civil infrastructure. Infrastructure failures (and absences) leave humans in the position of contending with nature in the raw. However, with foresight, planning, and preparation hopefully the infectious disease consequences can be minimized.

A Paean to Pharmaceutical Innovation: A Review of Miracle Cure


When you think about the power of the human mind to solve problems, it is difficult to overestimate what impact the discovery of antibiotics have had for the human race. They almost single-handedly rendered many deadly infectious instantly benign (of course until antibiotic misuse exacerbated resistance). While many people know the story of the moldy petri dish, there is a lot more to tell. William Rosen, in Miracle Cure: The Creation of Antibiotics and Modern Medicine, tells that story expertly.

This book, published earlier in the year, spans the entirety of modern medicine using antibiotics as the lens from which to view the field. This might seem odd as antibiotics represent only one component of medicine but Rosen shows just how their discovery changed the game.

The discovery of antibiotics was scientifically dependent on many antecedent discoveries regarding the causes of disease, microscopy, the theory of the cell, and the search for magic bullets to name but a few.

Once antibiotics were discovered, the fact that a "miracle cure" with true efficacy (unlike patent medicines, folk remedies, and homeopathy) a whole structure of medicine that could actually do something to ameliorate illness was created. And with that the need for randomized controlled trials, rational drug design, and the pharmaceutical industry. Indeed, Rosen states that "the machine of pharmaceutical innovation...wouldn’t exist, would never even have been built, but for the antibiotic revolution”

Rosen is clearly thankful and appreciative (as am I) for the innovators in pharmaceutical firms that made miracle cures like antibiotics possible. As Rosen aptly writes, "Tens, perhaps hundreds, of millions of victims of a thousand diseases from leukemia to river blindness are alive and thriving entirely because of a drug breakthrough. For them, and especially for the literally uncountable number of people whose bacterial infections, from strep throat to typhus to anthrax, were cured by a ten-day regimen of antibiotics, the bargain probably seems an extraordinarily one-sided one.”

Miracle Cure takes you from contemplating Galen's ideas about the four humors all the way to thinking about aplastic anemia caused by chloramphenicol -- a difficult task the book accomplishes excellently. I highly recommend it to those interested in the history of medicine, the history of the pharmaceutical industry, and the world of infectious diseases.

DA Henderson's Legacy Will Continue


One year ago, the world lost one of its benefactors, Dr. DA Henderson. I've written about DA's incredible career and insights before and I will continue to do so as his prowess was, in my estimation, without equal. 

DA was the architect and commanding general of the WHO's smallpox eradication campaign -- the one and only successful effort to rid humanity of an infectious disease. His merciless assault on the virus gave it no quarter and gave humanity new hope that they would never again be haunted by this virus and that such feats as the eradication of an infectious disease eradication were possible with the use of one's mind. 

DA's ability, his field vision, with infectious disease is what I think the world will miss the most. He had developed the ability to see an infectious disease outbreak with such precision as to transcend the predictions and assumptions of mathematical models. It was as if he and the microbe were looking each other in the eye, each anticipating the other's move. 

What I miss most,  is his unending enthusiasm for infectious disease and his boundless energy to infect others with that enthusiasm while imparting priceless wisdom.

In the Center, his portrait hangs on the wall and one can look at it for inspiration and ask "What Would DA do?"

WWDAD about the scary changes with H7N9 avian influenza, the ongoing cases of MERS in the Arabian Peninsula, the whispered threats of North Korean biological weapons, the longer chains of human to human monkeypox transmission, Candida auris, the roll out of a malaria vaccine, the ongoing spread of cholera in Yemen, the recognition of Zika as a teratogen, and so many of the challenge our species will continue to face from the microbial world? 

We will never know the answer to that question and we are all worse off for it. But, we do know that DA's brilliant legacy lives on in all those infectious disease physicians, microbiologists, public health practitioners, epidemiologists, and world leaders who had the opportunity to learn from him.

The fact that DA existed, succeeded against incredible odds against smallpox, and told us all how to approach the field gives our species an incredible tool we can use to flourish in this microbially-dominated planet.

This Pig is not a PERV: Major Xenotransplantation Advance

One of the most exciting fields of medicine which represents the integration of several disciplines is organ transplantation. The advances that have made such an innovative and life-enhancing feat possible were the result of breakthrough insights by heroic pioneers in the life sciences. However, despite the feasibility and almost routine nature of solid organ transplantation today, the full benefits have not been achieved. It is basically universally known that there are not enough organs procured per year to meet the needs of those on waiting lists. Several partial solutions have been proposed including more efficient allocation algorithms, increased public outreach campaigns to increase organ donation, and the use of "high risk" organs but even with all these initiatives combined demand is still outpacing supply. 

Using organs from animals closely related to humans -- such as pigs -- has been a proposed fix that has, unfortunately, not been able to reach fruition for several reasons. One reason xenotransplantation from pigs has been stalled is the presence of viruses integrated into the chromosomes of the pig. The fear is that porcine endogenous retroviruses (PERVs) could reactivate in the transplanted human, as several viruses can do in the presence of immunosuppression, and cause unknown effects which may be benign or not. A xenozoonosis would have major implications as it would virtually unprecedented, with no treatment protocol (though HIV drugs may work), and unknown contagiousness. To date, pig heart valves, pig skin, pig-derived insulin, and encapsulated pig islet cells are being used in humans with no evidence of PERV infection. 

A team from Harvard, which included the visionary George Church, recently harnessed the power of CRISPR to clean pig DNA of these viruses and allow PERV-free piglets to be borne. The study was published in Science. This is an unequivocally major achievement and has removed a major roadblock while illustrating the enormous value of CRISPR in furthering human life. 

Now that this hurdle has been cleared, it will be necessary to ensure that the human immune system is not too aggressive in rejecting the organ, which will need some further genetic modification in order to not tip off the immune system to its origin.

There is no timeline for how long it will be before pig xenotransplantation is adopted on a larger scale as protocols and regulations that govern these procedures will have to be rewritten, but each step forward should be applauded.