Category Archives: terminology

Contagion and Pestilence in Isidore of Seville’s Etymologies

Saint Isidore of Seville (c. 560–636). Bishop, confessor and Doctor of the Church. Altarpiece of Saint Isidore. 15th century. Diocesan Museum of Calatayud. Spain.

Before Isidore of Seville became the patron saint of the internet, he was known for over a thousand years as a font of knowledge.  Isidore was not an innovator; he was a master of synthesis. It is through Isidore that we have an orderly account of the learned knowledge of the Late Roman world.  He was conscious of the fact that he was saving information at risk of being lost.  His Etymologies, written in twenty sections between 621 and 636, was both the Latin dictionary and encyclopedia of the entire medieval period. Isidore is not always correct — there is a lot of sounds-like etymology– but his explanations were accepted throughout the medieval period. So, Isidore is an ideal source to gain an understanding of how modern terms like contagion and pestilence were defined from the early seventh century in the midst of the first plague pandemic.

From Book IV: On Acute Illnesses:

17. Pestilence is a contagion that as soon as it seizes on one person quickly spreads to many. It arises from corrupt air and maintains itself by penetrating the internal organs. Although this is generally caused by powers in air, it never occurs without the consent of God. 18. It is called pestilence (pestilentia) as if it were pastulentia, because it consumes (depascere, ppl. depastus) like fire, as Vergil, Aen. 5.683): The pestilence descends on the whole body*. Likewise contagion (contagium) is from ‘touching’ (contingere), because it contaminates anyone it touches. 19. The swellings (inguen) (ie. bubonic plague) are so called from their striking the groin (inguen). Pestilence is also called plague (lues), so called from destruction (labes) and distress (luctus), and is so violent that there is no time to anticipate life or death, but weakness comes suddenly together with death. (p. 110-111).

The general definition of both pestilence and contagion, along with their spellings in Latin, are recognizable to us today. The modern editors note that Vergil is using pestilence as a metaphor for the burning of a Trojan ship. It is on the origin or mechanism of pestilence where we differ. Isidore’s world understood medicine as a function of airs and humors, a topic for another time. He also writes of plague again in his On the Nature of Things, which was less influential than the Etymologies. In a later post I will look at what the Venerable Bede does with both the works of Isidore and Pliny in his own On the Nature of Things.

Inguen as the term for a swelling in the groin is the what draws my attention. Inguen is the root for the modern word inguinal; as in inguinal bubo.  Two of the most important European historians of the first pandemic, Gregory of Tours and Paul the Deacon, used the term inguinaria for the pandemic. Unfortunately, inguinaria is usually literally lost in translation. Rather than leaving inguinaria as the early medieval term for bubonic plague, it is usually translated as the less specific ‘plague’ or a little better ‘inguinal plague’. Even in the translation above, it is translated as swelling with the original word in parenthesis.

Bubo is likewise said to come from the Greek word for groin, boubon (βουβών), but I have not found a source to discuss its earliest use. Isidore does not discuss the term bubo or the Greek term boubon, presumably using inguen instead. Greek boubon translates into Latin as inguen, both meaning groin or swelling the groin. Ironically “inguinal bubo” then duplicates the same meaning. It would be interesting to know if boubon or bubonic is a word used for the first pandemic (541-c. 750) in the Eastern Roman empire.

One of the important inferences from the derivation of inguen/boubon is that it supports the groin as the primary site of early infection. So while buboes can be found in the axilla and neck, and there are other transmission routes, it was recognized from the beginning as a disease of the groin. This in turn supports fleas as the primary transmission vector, since as insects found on the floor most of the time, they usually bite on the legs resulting in an inguinal bubo.

Reference: Barney, SA, Lewis, WI, Beach, JA, and Berghof, O. (trans and ed). The Etymologies of Isidore of Seville. Cambridge, 2006.

Demystifying Scientific Authorship

Over the last few months, I’ve been talking quite a bit with historians. Many of them are starting to read more biology papers; some are perplexed by the format and brevity. So, I plan on occasionally writing posts that I hope will help non-science folks and students cope with science literature.

A recent question:  how can a paper have ten or more authors? Who is in charge of the project?

A science paper is not an essay like a history or literature publication. Its is a research report representing the work of a whole team. There are very few soloists in science.   In some ways “authorship” is really not the right term for the names on the report, but it is historical convention.

There are no hard and fast rules for who is named on a paper or their order. However, names can be classified in four groups in relatively this order  on papers with more than four  authors.

  • First author: recognition of  the person who has done the most bench work. First authorship is important in the development of a researcher because it shows that they have accomplished new laboratory experiments and can do the daily management of experiments. The first author is usually a grad student or post-doc (post-doctoral fellow). When there are multiple authors (>4), the first author is never the project leader.
  • Research contributors: other members of the team including research assistants, post-docs, and other grad students. Research assistants are finally getting recognition for what is often a career long commitment to a project.  Specialists who provide unique services like pathologists or bioinformatics/ computer specialists may also be included here. Ultimately it is the principal investigator who determines which other members of the team are recognized on the paper.
  • Materials contributors: providers of unique materials that are vital to the project. Examples of material contributors include physicians who collect patient specimens, archaeologists who provide access to bones or teeth, or molecular biologists who provide a vital clone or research organism (like a specially bred rat etc).
  • Principal Investigator, usually called the PI,  is the person responsible for the project on federal grants. They are the project director. Roles of the PI include research direction and administration,  recruiting, funding, and outreach to the scientific community as much as the public. They are always the last author listed on publications and usually designated as the corresponding author. When in doubt, always go with the corresponding author as the project leader.

For large multi-center studies, like some of the recent plague genetics papers, there can be multiple PIs (designated by multiple corresponding authors) and the recognition of more than one ‘first author’ (notation that multiple people contributed equally). Some newer publications will have some indication of who contributed to what. It is fairly unusual for any one person to be designated as the author (writer) of the paper, even though there is usually one primary writer.

With fewer than four authors it is nearly impossible to predict roles unless you know the individuals named. Go with the corresponding author as the project leader.

Hopefully, this has helped demystify scientific authorship. Comments and questions are always welcome!

Leptin: Linking Malnutrition and Vulnerability to Infection

The correlation between malnutrition and vulnerability to infection has been well established (discussed previously here). While the immune dysfunction could be characterized it was not until the last 10-15 years that an exact mechanism began to resolve.

It all began with the discovery of a new hormone called leptin from an unexpected place, adipose tissue (fat cells). Leptin, a product of the obese (ob) gene, was discovered while looking for factors that regulate body fat. As a consequence of manipulating this gene in an attempt to regulate body fat, it was discovered that mice deficient in leptin had profound immune deficiencies.

The amount of leptin produced by adipose cells (fat cells) is directly proportional to the amount of fat in the cells. (The number of fat cells in adults does not change,  their size just shrinks or swells.) Leptin levels drop as body fat decreases or during fasting. Once leptin levels fall below a threshold, the lack of leptin puts the mammalian body into a starvation response. Areas of leptin activity are signaled by the production of the leptin receptor (OBR gene). Tissues producing the leptin receptor include areas of the hypothalamus that regulate body weight, bone mass, and appetite; ovarian cells, beta-cells of the pancreas, endothelial cells, and bone marrow stem cells, macrophages, and lymphocytes (1). Leptin influences cellular function by directly interacting with peripheral tissues including immune cells in lymph nodes, bone marrow, pancreatic function and bone homeostasis, but also by triggering hormonal changes in the brain, specifically in the hypothalamus. Study of leptin levels has opened previously unsuspected linked between central nervous system control and the development of the immune system.

The Hormonal Trigger of the Starvation Response

Leptin’s control of metabolism and the  immune system. (Ref. 2)

As long as leptin levels stay within normal levels, all of the functions displayed above function normally. As the leptin levels drop, many of these functions are adversely effected. It is a wide-spread trigger for a starvation response.  Why cripple the immune response during starvation? My best guess would be because of the huge energy expenditure required to keep the immune response running normally, especially in cellular proliferation.

When leptin levels drop too low, physiological dysfunction occurs in haematopoiesis (blood cell production), bone metabolism, glucose metabolism and angiogenesis (blood vessel production and maintenance) and immune suppression involving both the innate (non-specific) and adaptive immune system. During malnutrition, the size of the thymus gland shrinks with diminished T cell development. This may be one of the long-term consequences of childhood malnutrition. Children with congenitally low leptin levels have a higher mortality rate due to childhood infections (2).

Leptin modulates immune function (ref. 1)

With all the functions illustrated above, it’s not very surprising that malnutrition is the second most common cause of secondary immune suppression today (2). Alternatively, high leptin levels in obese people have also been linked with increased vulnerability to infection possibly through the development of leptin resistance due to prolonged exposure to excessively high levels of leptin (2). Food for thought considering that obesity was one of the only risk factors for a poor outcome during the recent H1N1 influenza pandemic. We have come to expect malnutrition induced immune suppression, but we may also have to consider over-nutrition induced immune suppression and/or autoimmunity as outcomes of immune dysregulation due to leptin resistance.

References:

[1] La Cava, A., & Matarese, G. (2004). The weight of leptin in immunity Nature Reviews Immunology, 4 (5), 371-379 DOI: 10.1038/nri1350

[2] Procaccini C, Jirillo E, & Matarese G (2012). Leptin as an immunomodulator. Molecular aspects of medicine, 33 (1), 35-45 PMID: 22040697