Sherlock Holmes: Proto-Infectious Disease Physician

"I love the detective work."

That's the answer I give when people ask me how I chose infectious diseases as my subspecialty. Detective work in infectious disease involves reasoning from the perceptual level, according to the laws of logic, to arrive at a diagnosis and formulate a treatment plan. This method, which has both deductive and inductive aspects, is not exclusively applicable to medicine, but all of life. One realm, however, where it is employed in a striking manner is in forensic science and the practitioner par excellence is the fictional Sherlock Holmes who, fittingly, was the creation of the physician Sir Arthur Conan Doyle. 

Not surprisingly, when I came across the book The Remedy: Robert Koch, Arthur Conan Doyle & the Quest to Cure Tuberculosis, I had to read it immediately. This excellent  book was written by former Wired executive editor Thomas Goetz, now CEO of the innovative health data concern Iodine. The book is focused on two seemingly disparate topics that Goetz expertly weaves together into a cohesive and illuminating whole: the evolution of the germ theory of disease and its intersection with Sir Arthur Conan Doyle.

Tuberculosis can scarcely be mentioned without thinking of Robert Koch, the Nobel Prize-winning physician. Koch definitively proved that the dread disease was caused by an invading pathogen, Mycobacterium tuberculosis. Such a discovery provided further evidence of the veracity of the germ theory of disease, which was catapulted from fringe hypothesis status by Louis Pasteur. Koch's contributions to the study of tuberculosis, anthrax, cholera, and other infectious diseases--in my view and in Goetz's--pale before the enormous feat he performed in developing and articulating his eponymous postulates. The postulates form the basis for proving a pathogen is the cause of a disease in question. This achievement, as Goetz recognizes, cannot be understated.

The other strand of the story told is that of Sir Arthur Conan Doyle, a physician in practice who longed to be a writer. Goetz writes of how Doyle employed his medical worldview, which consisted of meticulous observation coupled with deductive reasoning, to create the character of Sherlock Holmes, who first appeared in two early novels. However, Holmes ascended as a celebrity in his own right after a fascinating incident: Koch's mistaken claim regarding tuberculin. What Koch claimed was that tuberculin, a glycerin extract of M.tuberculosis now in common use in tuberculosis skin testing, was a remedy for tuberculosis. Doyle, dispatched to Germany as physician correspondent for an English paper, was unconvinced of the data behind this claim and his subsequent article helped to publicize the errors behind what came to be a scandal over tuberculin. Doyle soon fully committed to writing and left medicine; Sherlock Holmes soared to the point that he even eclipsed his creator. 

The book also contains many historical gems, provides a thorough treatment of how the germ theory increasingly gained acceptance one mind at a time, and concretizes how medicine (and detective fiction) was revolutionized. 

I highly recommend it.

How to Tame a Virus- A Review of *Paralyzed with Fear: The Story of Polio*

Polio is an infectious disease that holds a special allure for Pittsburghers. It was here that Jonas Salk conducted the research that led to his famous vaccine, forever changing the relationship between humans and this virus. I often imagine what it must have been like to witness Dr. Salk's triumphant return to Pittsburgh--police escort and all--after the vaccine was shown to be efficacious. Dr. Salk's achievement, however, is not something that stands alone; it is part of a pantheon of scientific advances (not the least of which includes Albert Sabin's version of the vaccine). 

There have been many books written about this virus, Jonas Salk, and other aspects of the fight to rid the world of this virus. One such book cost me a considerable amount of money (and is now available for $3.50). 

I recently completed one of the newer additions to this growing library: Gareth William's Paralyzed with Fear: The Story of Polio. 

I really enjoyed this book primarily because it provided a broad, historical, inductively-based scientific approach to the topic. Instead of providing a simple chronological listing of the landmark achievements that led to the control of polio, Dr. Williams employed an approach that places the reader on the trail of scientific inquiry that painstakingly led scientists, step-by-step (and down some unfortunate blind alleys), to higher rungs in the ladder of knowledge which culminated in Eckard Wimmer's synthesis--from scratch--of polio in 2002. 

Some highlights of the book include: a description of the well-known rivalry between Sabin and Salk (which included a particularly nasty bit of correspondence in which Sabin wrote to Salk that "love and kisses were being saved up" for him); DA Henderson's discovery of vaccine-associated paralytic polio (VAPP) linked to the Sabin vaccine in the 1960s; the anti-vaccine movement's opposition to the vaccine; a thorough discussion of the discredited hypothesis of the polio vaccine being the origin of HIV; speculation that FDR may have actually had Guillan-Barre Syndrome (not polio); the "fear campaign" designed to spur public concern in the US over this disease, which was never as big a threat to US public health as other diseases; and countless other anecdotes that make for good reading.

As of today polio eradication remains a daunting task with 89 cases occurring in 9 countries this year, 2 of which are new to the list from 2013. Nigeria, Afghanistan, and Pakistan are the 3 most important heads of this hydra that must be decapitated if eradication is to succeed. It remains to be seen whether this eradication will be successful but one thing is certain: the polio vaccine and the individuals who created it, or whose work led to its creation, have thoroughly destroyed the ability of this virus to wage war on mankind. It only remains for humans to allow the destruction to be total.

Six Little Monkeys Aren't Jumping Any Longer

I just read about the death of 6 recently arrived tamarin monkeys at the Oregon Zoo. While I am by no means a veterinarian, the mysterious death of lower primates should make every infectious disease physician's ears perk up. 

The reason why unexplained outbreaks--epizootics--in lower primates are so important stems from the fact that if a pathogen is able to infect a monkey or chimpanzee, there is a good chance that it has the ability to infect humans, as all primates are genetically similar. 

In fact, preventing these diseases from spilling over--a concept made popular by David Quammen's book--into humans has become a major focus of interest in the emerging infectious diseases world. 

Integral to this paradigm is the simple concept of "One Health," a viewpoint that recognizes that  physicians and veterinarians have many of the same goals and that situational awareness of diseases of interest occurring in animal populations is crucially important to the task of safeguarding human health from infectious disease threats. Monitoring sentinel animal populations such as primates, bats, and poultry for infectious diseases can provide clues allowing some degree of predicting the pathogens on the cusp of jumping into humans to be possible. Similarly, monitoring human populations that have exposure to these species, such as bushmeat hunters and poultry workers, can provide early evidence of cross-species infections before a wider outbreak occurs. In fact, such monitoring would likely have shown HIV in its early years as an agent almost exclusively infecting bushmeat hunters and bushmeat preparers.  

While these monkeys, who were in quarantine because of their recent arrival, may have died from something common and not on par with the events detailed in Hot Zone, their deaths cannot be taken lightly and the cause should be determined. As a non-veteranarian it is difficulty to speculate on causes of death, but ruling out an infectious disease is paramount. 

Update: Seems like travel-related shock may have been the etiology.

Distracting Injuries & Complex Pathologies in my A/C

My air conditioner broke. Twice. Within one week.

What could that have to do with medicine and infectious disease? A lot, if you are as obsessed with these topics as I am. 

What I had a hard time understanding was how the HVAC repairman fixed the air conditioner on one day only to have it malfunction a few days later. To blame were two different components. After the first repair, since everything seemed to be working, there was no impetus to check for further issues in the system. A few days later, those other "issues" manifested and I was left with a sweltering condo. 

In medicine there is something known as a distracting injury. For example, if someone breaks her leg in a fall the pain may be so intense that the individual doesn't realize that her neck also hurts. So, physicians are encouraged to discount the patient's denial of pain in one body part if a distracting injury is present in another. In effect, my air conditioner had a distracting injury that the repairman exclusively focused upon, blinding him to the other issue. 

I also recalled something one of my favorite attendings said to me when I was an infectious disease fellow. It was her admonition that complex patients--such as the severely immunosuppressed--can have more than one pathophysiological process occurring within them.

Was my air conditioner immunosuppressed? 

The Ever-sharpening Spear Aimed at HIV

It's hard to keep track of the various strategies being employed to functionally cure HIV and their relative merits. A new book titled, Cured: How the Berlin Patients Defeated HIV and Forever Changed Medical Science by Nathalie Holt, does a great job at detailing these approaches and their histories.

The book weaves together the paths of the two Berlin patients, Timothy Ray Brown and his predecessor Christian Hahn, who experienced functional cures of their HIV infections. While the story of Timothy Ray Brown is familiar to many in this field (receipt of a bone marrow transplant for leukemia from a donor who possessed the HIV resistance mutation CCR5Δ32), Christian Hahn's story is equally fascinating.

Hahn was placed on anti-HIV therapy soon after infection and his regimen included an unusual drug, hydroxyurea, with unique properties. After stopping therapy Hahn did not have any viral rebound. Debates over whether it was the timing of therapy, the use of hydroxyurea, or another factor ensued. In the end, Hahn was found to harbor a protective genetic signature HLA-B*57 that can control HIV replication.

The book also covers other cure approaches such as that employed with the Visconti Cohort, the "Mississippi Baby" (and her offspring, the "Long Beach Baby"), and the failed approach taken with the "Boston Patients" who underwent non-CCR5Δ32 bone marrow transplants. See this great amFAR graphic for a guided tour of these cure approaches. 

I highly recommend this book to those interested in getting a glimpse of the cutting-edge science being employed in this Herculean effort.