Category Archives: A bit ‘o history

Three years of BIO230 blogging: how long can it go?

The cake is the truth!

Not enough candles on that cake anymore

This is an update of what is now an annual posting: October 24th is my anniversary for maintaining this forum as a supplement for the course/personal exercise in writing for myself. During this time, I along with three dozen students have generated almost 160 290 404 posts on pretty much any topic that happened to be of interest me at the time. It was important to me when I started this project that it would be a two-way mechanism of interaction, and the student comments and participation were of paramount importance.

I’ve had a number of postings that I’ve been particularly fond of over the past year. My new recurring feature follows the Centers for Disease Control’s “Notes from the Field” column, and there have been some excellent outbreaks over the past year.  I had an opportunity for a rant this past summer, which for long time readers was a followup to this time when I dropped the “F”-bomb in class, for excellent comedic effect. Student postings have also been very enlightening and fun, for instance this submission from Katrina this semester. And I am particularly proud of my mad ego-surfing skilz, as evidenced by this ode from an admiring student from last year. Note to all; feel free to continue to use Twitter tags #shitsingletonsays and #YCPMicro for new material in future semesters.

I’m looking forward to the next year and the coming discussions. Keep the comments coming, and if you find something neat about Microbiology in the news you’d like to let everyone know about, write it up and we can talk about it together!

Cell Biologists win the 2013 Nobel Prize!

I just saw the CNN story this morning about the announcement for the Nobel Prize in Physiology or Medicine. This year’s laureates are James Rothman of Yale University, Randy Schekman of the University of California, Berkeley, and Thomas Südhof of Stanford University. All three scientists have been classically trained cell biologists who have contributed tremendously to our understanding of the movement of material inside of living cells, which is a field I have been following for most of my scientific career (all 3 of these scientists appear in the bibliography of that paper from 1997).

I have been interested in Randy Schekman’s work for the longest, dating back to when I first started in graduate school at Case Western Reserve University in the late 1980′s. His lab was interested in dissecting the eukaryotic secretory pathway in the 1970′s, and used the model yeast Saccharomyces cerevisiae to help understand it. To accomplish this, he studied a panel of temperature sensitive mutants of yeast that had a very specific part of the secretory pathway blocked when you threw the on-off switch by raising the temperature. Because the mutants were at sequential spots along the pathway, if you made a double mutant (i.e. a mutant that had two mutations in the pathway), the resulting mutant demonstrated the phenotype of the earlier mutation in the pathway. By doing this, you could tease out the individual events in the secretory pathway using genetic tools.

I heard James Rothman give a seminar also when I was in graduate school, where he summarized the current understanding of the secretory pathway from a different perspective. Rothman’s lab was interested in the same thing but used a biochemical approach in mammalian cells. By growing large amounts of mammalian tissue culture cells and purifying individual protein components, these components could be added back together in a test tube to determine the way that they interacted with one another. I recall distinctly during Rothman’s talk when he described a tremendous moment of insight when it was realized that the genetic elements studied by the yeast cell biologists were essentially the same thing as the protein elements studied by the mammalian cell biologists.

I became familiar with Thomas Südhof’s work as a postdoctoral researcher at the University of Virginia in the mid-1990′s. His lab was interested in a phenomenon that we were also interested in: how does the process of exocytosis enable materials to be released from vesicles, specifically at the synapse of a neuron? He also used a biochemical and cell biological approach to purify components of synapses and reconstituted them in vitro to dissect the parts of the pathway. He was particularly interested in a difficult problem in cell biology, which was to understand how two distinct membranes could be fused together. This problem is not trivial. Although one would think that two hydrophobic membranes might readily associate easily with one another, it is hard to rearrange the separate lipid bilayers in two membranes to bridge each other and fuse.

All three researchers have been recognized today “for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells” using parallel approaches in genetics, biochemistry, and cell biology. Science of course builds on the work of others, and this recognition today echoes the 1999 Nobel Prize awarded to Günter Blobel, and the 1974 Nobel Prize to Albert Claude, Christian de Duve, and George Palade. Today’s recognition highlights our ever deeper understanding of the fundamental relatedness of all living things.

Happy Birthday, Julius Petri!

GoogleIf you were like me, you probably got up today and said “It’s about time that Google recognize the great science of Microbiology with a Google Doodle!”

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.

The English Sweating Sickness

Portrait of Anne Boleyn, Henry's second queen;...

Portrait of Anne Boleyn, Henry’s second queen; was sick with illness in July 1528. (Photo credit: Wikipedia)

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.

Sometimes you’re wrong

Oliver Wendell Holmes in 1853, via Wikipedia

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?

It’s too late for your teeth


teeth (Photo credit: jfraser)

Angela (3 PM Micro) told me she would be late for class on Wednesday, due to a dental appointment, and I told her about this news alert from describing research from Nature Genetics. (Sorry, paywall!) Scientists at Australia’s University of Adelaide isolated preserved dental plaque from excavated human remains covering  a range of 7500 years, buried in Northern Europe. DNA was isolated from the preserved remains that gave a snapshot of the microorganisms living in the human oral cavity during different historical eras, and that DNA was analyzed to determine the diversity of those organisms.

The interactions of organisms in the mouth, and their relative ability to cause disease is nothing new. Longtime BIO230 fans may recall this posting from March 2011, which proposed a novel way to inhibit tooth decay by introducing a new bacterium into the mouth. This current report indicates that dental caries may be a very new problem in human health, and that it may coincide with the development of agriculture and the concurrent shift in human diet to one richer in carbohydrates. The researchers found that the diversity of microorganisms associated with the mouth have significantly decreased in phylogenetic diversity over the past 7500 years, and today’s mouths are much more heavily colonized by Streptococcus mutans, a species that is the primary agent in dental caries.

ng.2536-F3The researchers characterized two shifts in microbial diversity in the oral cavity, the first several thousand years ago coinciding with the introduction of agriculture and the shift in human diet, and another one 150 years ago during the Industrial Revolution. It was at this time that processed sugars and flour became widely available throughout society. The most significant decrease in microbial diversity occurred at this time, as the figure shows. The authors of the study argue that the human mouth exists in a constant diseased state in modern times, in large part attributable to the loss of bacterial diversity and the dominance by caries causing strains.

The comment thread on i09 then degenerated into an argument detailing the virtues and drawbacks of the paleo diet, as a possible way to “regress” the oral microbiome to a state resembling those that ancestral humans might have had.  There are very few peer-reviewed articles looking at the positive and negative effects of altering the diet to make one rich in protein/lacking processed grains. One review article from 2009 summarized controlled human studies, and found that there were “promising” results, but no clear cut benefits from such a diet, and furthermore that the limited diet could actually be detrimental due to lack of vitamins and calcium. Additionally, a broad metagenomic analysis of the human gut microbiome indicated that there is actually not a large diversity of organisms between distant geographical locations. Humans show shifts in the microbial flora during different times in our lives (or perhaps age-related changes are due to the organisms influencing us), however there was no real correlation with different groups of microorganisms with any particular cultural group. That latter study strongly argues that there is very little we can do to broadly influence our microbial flora with any degree of success.


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