Category Archives: A bit ‘o history
Google today is commemorating Jonas Salk’s birthday with a Google doodle. Salk was the developer of the first vaccine against polio, a disease which affected 58,000 people in 1952 in the United States alone, leading to over 3000 deaths and over 20,000 people with permanent levels of paralysis from the disease. Polio is a viral disease, and is passed from individual to individual via contaminated drinking water, and until the development of a vaccine it was essentially impossible to control. Previous attempts at creating vaccines generally used a strategy of attenuating pathogens, a method of laboriously reducing the virulence of the pathogen in the laboratory, with the hope that non-virulent organisms might still provide protection against the more virulent pathogens in the wild. Salk’s innovation was to pursue inactivated pathogens; virus that had been grown in the lab, and then was partially denatured so that it was then physically unable to cause disease. Fortunately, this approach worked for Salk, and in 1955 the first polio vaccine came to market worldwide. By 1962, the number of polio cases in the US had dropped to under 1000, and the last case of natural transmission domestically occurred in 1979 during an outbreak among several Amish communities.
Salk was hailed as a hero when the wide availability of the vaccine was announced. The Google doodle above is based on an actual photograph from 1955–I think that people today have little understanding how terrifying many infectious diseases were to society as a whole. Salk was recognized with many honors during his career, however he did not receive the Nobel Prize even though he was nominated during the late 1950’s. Vincent Racaniello at the Virology Blog suggests that the prevailing opinion among the community at the time was that Salk’s procedure didn’t really involve true innovation, which is an important component of the Nobel Prize. The 1954 Nobel Prize was awarded to a trio of polio researchers (John Enders, Thomas Weller, and Frederick Robbins) who discovered a method to grow polio virus in the laboratory. Indeed, without this innovation, Salk would have never been able to produce his vaccine.
I came across a second item about polio this morning as I went through my Twitter feed, linked to by @popehat, a politics/news site that helps me to get outside my political comfort zone on occasion. In this Boston Globe article detailing what is hopefully the final days of polio here on Planet Earth, the intrusion of world politics clearly is complicating global eradication efforts. Most recent outbreaks have been limited to a small geographic area in sub-Saharan Africa, however Pakistan is currently experiencing an epidemic, whereas neighboring India has been certified “polio-free” effective this year. The problems in Pakistan have been complicated by US anti-terror efforts in the region. Currently, Taliban leaders regard legitimate polio aid efforts as suspect, with vaccination efforts as an American plot to deliberately infect children or to gather intelligence information. The latter suspicion is not off base, as in 2011 CIA operatives used a vaccination program around Abbottabad near Osama bin Laden’s compound to collect DNA samples in hopes of confirming that bin Laden was there. Following exposure of the CIA’s involvement, later vaccination aid efforts were stymied, and aid workers have been threatened.
Global polio eradication will eventually occur, and like smallpox, within a generation the only place polio virus will be found will be in laboratories. Smallpox required an almost 200-year concerted effort to eliminate; polio by contrast has essentially disappeared within two generations. This story however is important to remind us that seemingly disconnected events (the war on terror, global public health measures) are in fact tightly intertwined. Unfortunately, the messy intrusion of politics into polio eradication has created a mistrust of the importance of public health measures outside of this county. I fear that this same mistrust is also at work with public health measures here at home.
The last day of May is the birthday of Julius Richard Petri (1852-1921), who is generally acknowledged as the inventor of the Petri dish. This little device enabled microbiologists to easily culture and subculture microorganisms in the laboratory, which in turn allowed microorganisms to be easily isolated in pure culture for the purposes of identification. Petri was trained as a physician, and while on active duty as a military physician, was assigned to the Imperial Health Office in Berlin to work as an assistant to Robert Koch. Just prior to this, the Koch laboratory had begun to culture bacteria on solid media containing the solidifying agent agar. Petri’s innovative dishes allowed microbiologists to utilize aseptic technique during the transfer of microorganisms, greatly decreasing the chances of contamination of samples and thereby making the process much more effective. Petri’s original dishes were made out of glass, and were decontaminated by autoclaving after use and carefully cleaned for reuse. In the disposable BIO230 generation, our Petri dishes are made out of plastic and go out with the trash after decontamination. Although students might be able to save tens of dollars on their college tuition by going back to the reusable glass Petri dishes, I suspect that the busy life of the college student would make it a difficult proposition to require them to wash all of their own dishware to save a buck.
I came across a review article entitled “The sweating sickness in Tudor England: a plague of the Renaissance,” which was published in the journal Hektoen International. Outbreaks with these signs and symptoms were described periodically in historical accounts throughout the 15th and 16th centuries, but has not reappeared since. Descriptions of the outbreaks can potentially shed light on the basis of the disease. The outbreaks were renowned for the speed with which they arose, as well as how quickly they disappeared. Additionally, it seemed to be an English malady exclusively.
An eyewitness description by Richard Grafton in 1569 stated:
A new kind of sickness…through the whole region, which was so sore, so painful and sharp, that the like was never heard of to anyone’s remembrance before that time.
The main signs of the disease were pronounced sweating, flushed appearance, headache and other pain, which repeated several times as the disease recurred. Death was frequently due to dehydration.
Charles Creighton, in his History of epidemics in Britain, noted that the initial outbreak of the sweating sickness coincided with Henry VII’s invasion of England to take the crown from Richard III in 1485. Much of Henry’s army was composed of French mercenaries, who potentially were carriers of the disease. Creighton postulated that populations from continental Europe including France were essentially immune to the disease, due to generations of prior exposure. The isolation of the British Isles resulted in a population that had no previous exposure to the agent, so that when Henry brought the French troops into London, they also brought an infectious agent that the population had no innate defenses against. This resulted in periodic outbreaks that ravaged the population for a period of time until a measure of immunity was built up.
Several historians have postulated on the nature of the infectious agent, but no clear consensus has emerged to match a specific pathogenic agent with the described signs and symptoms. McSweegan in 2004 noted the similarity between reports of sweating sickness, and the presentation of disease during the anthrax terrorist attacks of 2001. Analysis of buried remains could implicate the presence of anthrax spores in tissue, a technique which has previously effectively been used to map the change in virulence of the agent of Bubonic Plague. Other investigators have noted the similarities between sweating sickness and presentation of disease due to hantavirus, or any of a number of arbovirus-based diseases such as Yellow Fever.
To date, no clear front runner candidate pathogen has emerged to explain the origin of the outbreaks. The speed with which it emerged as well as how it vanished suggests that it was a novel infection to the population, that was introduced by a rapidly growing population that had little innate resistance. Remains of victims with demonstrated provenance might help to shed light on potential causes of the disease, however many agents (particularly viral agents) would likely not be in recoverable form at this point.
Riki Gifford-Ferguson (11 AM Micro) thought I was wrong, and it turned out she was right! For her diligence, I hereby award House Gryffindor a special Bonus Point. The discussion came about during my overview of the work of Ignaz Semmelweis, and the origins of public health measures. I won’t rehash the story of Semmelweis beyond briefly summarizing it; for a more in depth discussion, here is a link to a previous blog posting. Semmelweis charted the incidence of puerperal or childbed fever, in two Viennese hospitals during the early 1840’s, and noted a significant difference in the number of cases. From this data, he instituted infection control measures that essentially eliminated puerperal fever, and ultimately published his results in a lengthy monograph in 1861. His conclusions were not well received, and he was apparently tricked into being committed to an insane asylum in 1865. He died later that year after a beating.
Riki remarked in class that she thought Oliver Wendell Holmes (1809-1894) had provenance in the link between medical practice and puerperal fever, and pointed me to his story. I was not aware of Holmes’ role in medical research, but instead knew of him as an essayist and poet. It turns out that Holmes also postulated the role of the health care worker in transmitting puerperal fever between patients, and indeed published a monograph in The New England Quarterly Journal of Medicine and Surgery in 1843. This article essentially went unnoticed, and was republished in 1855 in expanded form several years before Semmelweis’ publication. Interestingly, Holmes first clue to the link between physician and sick patient was hearing about another physician who died a week after performing a postmortem exam on a woman with puerperal fever. This was an ‘Aha!’ moment very similar to that experienced by Semmelweis at just about the same time. I cannot find any indication that Semmelweis was aware of the work of Holmes at this time, which is not surprising, given the extremely low profile of Holmes’ 1843 publication.
So what about medical outcomes? Sadly, the recommendations by either man were not broadly accepted by their respective medical communities, and both were largely ridiculed by their colleagues. Semmelweis died before he could be vindicated, but Holmes at least was able to live to see the recognition of the Germ Theory of Disease during the latter part of the 19th century. At the time, Holmes argument of the link between physician and patient resulted in no changes to medical procedure. His recommendations (purification of surgical instruments, burning of clothes following a fatal delivery, not practicing medicine for 6 months following a case of puerperal fever) were not adopted. In contrast, while Semmelweis was in charge of the maternity clinic in the Vienna General Hospital, he was able to institute control procedures that immediately resulted in a drastic improvement in patient outcomes, and a maternal mortality rate very much in line with what we see today.
UPDATE: Yikes! A ton of Facebook referrals here this morning! Was this article re-shared by someone?