Just in time for Chanukah! The Eleventh Plague: Jews & Pandemics from the Bible to COVID-19

It is with great excitement that Talmudology announces the release of my latest book, The Eleventh Plague: Jews and Pandemics from the Bible to COVID-19. In the US, the book is available on Amazon (two-day delivery!) where you can read the introduction and the first chapter. So buy it for yourself and get a copy for a loved one for Chanukah. (Or Christmas. Or Kwanzaa.) For some reason, Amazon is not currently delivering it to Israel. In the UK, the book will be released in March, so you will have to wait. Though I guess you could buy the e-book.

The book is packed with utterly fantastic material and historical events that have largely been hidden until now, and it tells the story of how infectious disease and pandemics have shaped and reshaped Jewish life. It was an absolute pleasure to write, and my research days would end with me announcing “…you’ll never believe what I found today!” (Thanks Erica, for being a good sport. And for believing.) Some of the background material was first published here on Talmudology, and it grew (and grew) from there.

Here is the table of contents, to whet your appetite:

“When I began the work, I did so with no hypothesis to test. I simply let
the sources speak for themselves, and any conclusions came later. What
I uncovered— much to my surprise— was the profoundly deep way in which
pandemics have impacted the story of Jews and Judaism. It was a story of which
I was completely unaware, despite being a physician and having a lifelong familiarity with Jewish sources. I discovered not only how Jews have been affected
by pandemics but also how they shared their encounters with their non-Jewish
neighbors. It was a common story but told in different dialects.”

— Jeremy Brown. The Eleventh Plague; Jews and Pandemics from the Bible to COVID-19. New York, OUP 2023. p.3

You can buy the book on Amazon, and also directly from the publisher with a 30% discount. Just click the images below.

The Eleventh Plague: Jews and Pandemics from the Bible to COVID-19 Buy on Amazon

Many thanks for your support.

And a Happy Chanukah from Talmudology

Nedarim 50b ~ Shmuel, Colonoscopies, and the Pillcam

Shmuel: Astronomer and Doctor Extraoirdinaire

Shmuel (c. 165- 257 CE) was a fascinating talmudic rabbi, who lived in Nehardea in Babylon. (Nehardea is located in what is today Anbar province in Iraq, and was under the control of ISIS until 2017. Heritage visits are therefore not recommended.)  Shmuel's areas of special interest were medicine and astronomy. He taught that all illnesses could be traced to "the air"  (הכל ברוח)  - or as we might put it today, the environment - and although he was a modest man, he was certain of his medical and astronomical skills.   He claimed to know the cure for  all but three medical conditions, (...כל מילי ידענא אסותייהו לבר מהני תלת) and he declared that he knew astronomy so well that the stars of the sky were as familiar to him as were the streets of Nehardea where he lived.

“Although I am as familiar with the paths of the stars as with the streets of Nehardea, I can not explain the nature or the movements of the comets..”

— TB Berachot 58b

Abdominal Pains? Swallow This...

In today's page of Talmud, Shmuel offers another of his medical teachings - a way to diagnose gastrointestinal disorders.  

 מאי ביצה טורמיטא? אמר שמואל עבדא דעביד לה שוי אלפא דינרי! ומעייל לה אלפא זימני במיא חמימי ואלפא זימני במיא קרירי עד דמתזוטרא כי היכי דבלעיתה. ואם אית כיבא סריך עלה וכד נפקא ואתיא ידע אסיא מאי סמא מתבעי ליה ובמאי מתסי

What is meant by a turmita egg? Shmuel said [that it is such an important diagnostic tool] that  a slave who knows how to prepare it properly is worth a thousand dinars.  He puts the egg into hot water a thousand times and into cold water a thousand times, until the egg has shrunk so that it may be swallowed whole.  If a person has a stomach illness, a residue forms over the egg, and when the patient excretes it, the egg can be examined and the doctor will know which medicine is needed and how to heal the patient....(Nedarim 50b)

All this may seem rather fanciful, but Shmuel was trying to solve a huge problem: when we want to understand how the gastrointestinal system is functioning, how do we look at, and get information from a place where the sun don't shine?  Shmuel devised a remote probe - in his case a hard-boiled egg - to send in and retrieve the necessary information. Two thousand years later, an Israeli medical device company has updated this idea, and in so doing has revolutionized the way we can investigate intestinal disorders.

The Israeli Pillcam - Shmuel's Idea in Action 

One way that your doctor can figure out what is wrong with your gastrointestinal system is to take a look. For a many years, that meant sedation and inserting a scope the width of your index finger down the mouth and into the stomach, or up the rectum and into the colon. But an Israel company has changed all that, using Shmuel's idea (sort of).  Given Imaging, based in Yokne'am, has developed a pill which contains a camera capable of sending high quality images from the depths of your guts straight to your doctor's computer. You just swallow the pill and let it send images from deep inside you.

Normal colon and findings visualized at colon capsule endoscopy. A: Normal colon; B: Diverticula; C, D: Polyps; E, F: Ulcerative colitis. From Spada et al. Colon capsule endoscopy: What we know and what we would like to know. World Journal of  Gastroenterology 2014: 7; 20(45): 16948-16955.

There are of course limits to the pillcam technology - for one thing if a lesion is seen in the images, it will need to be biopsied, and that needs an old fashioned endoscopy exam.  But it is a wonderful option for GI doctors and their patients. Perhaps even Shmuel would have been willing to give up his very shriveled hard-boiled egg for the opportunity to swallow a new, shiny, white Israeli pillcam.*

[*Update: In 2014, Given was acquired by a private company, who later sold it to Medtronics.]  

Nedarim 41~ The Strange Story of Theriac

Theriac pot, 1782, from here.

In today’s page of Talmud, there is a discussion of the benefits of a fever, which we reviewed in our previous post. It is during this that Rava chimes in:

נדרים מא, ב

אָמַר רָבָא: הַאי אִישָּׁתָא, אִי לָאו דְּפַרְווֹנְקָא דְּמַלְאֲכָא דְמוֹתָא, מְעַלֵּי כְּחִיזְרָא לְדִיקְלֵי, חַד לִתְלָתִין יוֹמִין, וְכִי תִּירְיָיקִי לְגוּפָאי

Rava said: With regard to fever [ishta]…it is advantageous if its incidence is once in thirty days, and it is like an antidote [tiraiki] for poison in the body…

What might this “antidote” be? In his famous dictionary, Marcus Jastrow, explains תִּירְיָיקִי in this way:

So today, we will delve into the strange history of this antidote tiraiki, better known as theriac.

Theriac is mentioned by the Rambam, (הל׳ חמץ ומצה 4:10) and in the Shulchan Aruch, the Code of Jewish Law. There we learn that should any chametz (unleavened bread) fall into your theriac on Passover, the mixture may be kept and used, despite the usual prohibition of mixtures of this sort. Good to know.

שולחן ערוך אורך חיים, 441

והתריאק"ה שנתן לתוכן חמץ מותר לקיימן בפסח שהרי נפסד צורת החמץ

In his commentary on our passage of Talmud, Rabbi Asher ben Jehiel (1250–1328), known as the Rosh, noted that theriac is made from all manner of spices. He would surely know this, because during the time in which he lived, theriac flourished. But theriac predated the Rosh by more than one thousand years…

The second century Greek physician Galen is thought to have authored an entire work De Theriaca ad Pisonem on the healing properties of theriac, and its use as an antidote to poison.

Where did theriac come from?

The word theriac comes from the Greek term θηριακή (thēriakē), meaning "pertaining to animals,” from another word θηρίον (thērion), meaning a wild animal. It is from this word that word “treacle” is derived. Theriac may have originated in the second century BCE., where legend has it that it was developed as an antidote against poisoning by Mithridates VI, King of Pontus. Actually, the king seems to have had an unusual interest in this antidote; he is thought to have tested it on prisoners condemned to death, and hence theriac was once known as mithridatium. The original recipe (and there are many) contained as many as forty ingredients, and over the centuries theriac was variously concocted using all manner of things, although the most frequently listed were viper flesh, opium, wine, honey and cinnamon. Theriac was used for perhaps some two millenia (!) until it declined in popularity in the 18th century. Here, for example, is the Latin theriac recipe of Paul Guldenius, printed in Thorn in 1630. (It is one of only two surviving copies, held by the Gdansk Library of the Polish Academy of Sciences.)

The printed Paul Guldenius Theriac recipe (Gdansk Library of the Polish Academy of Sciences). From Raj. et al. The real Theriac – panacea, poisonous drug or quackery? Journal of Ethnopharmacology 2021: 11

And here is the translated list of the Guldenius recipe:

Also from Raj. et al.

Jews, Theriac and the Black Death

During the terrible outbreak of bubonic plague in the middle of the fourteenth century, and the many that followed, theriac was recommended for its preventive and curative properties. For example, it was discussed by the Italian Jew Abraham ben Hananiah Yagel (1553– c.1624). He was by any definition a polymath. His works include not one but two lengthy encyclopedias, a manual of belief “audaciously adapted from a Catholic manual” and a work in praise of women. But Yagel was first and foremost a physician, and it was in this role that in 1587 he published his first work, a short tract on plagues called Moshia Hosim [The Savior of Those Who Seek Refuge]. “Do not fear the warmth brought on by theriac,” he wrote, “for in small diluted doses it cannot harm anyone.” Those who were sick should dress in clean, comfortable clothes “for they stimulate the sense of touch” and should be surrounded with sheets soaked in a mixture of vinegar and theriac, as well as fresh flowers and sweet-smelling roses “for they uplift the sprits of the sick.”

What should you take if theriac was not available? Good question. Yagel recommended urine:

…those who are learned about nature have taught that it is useful and good to take the urine of a young, handsome, and healthy boy, and to drink it each morning. It will filter out the bad air [that causes the plague].

Hold off your criticism. Yagel here was indeed reflecting the best of contemporary medical thinking. The German medical historian Karl Sudhoff (1853– 1938), who made a career studying almost 300 plague texts from the early Middle Ages, noted that in one Latin treatise on health written in 1405, “older patients who were sometimes counseled to drink a boy’s fresh urine might (understandably enough) feel some nausea.” And the Italian physician named Dionysus Secundus Colle who recovered from the plague around 1348 had this to say: 

I have seen women gathering snails and capturing lizards and newts, which they asserted that, once they had all been burnt down to a powder . . . they administered two drachmas of it in a boy’s urine, and they cured and persevered many, and afterward I was compelled to investigate [this cure myself] and afterwards I cured many.

Theriac was also thought to prevent infection. Jacob Zahalon (1630– 1693), the author of Otzar Hahayyim [A Treasury of Life] described his work as both a physician and a rabbi during an outbreak of bubonic plague in Rome in 1656. The plague arrived from Spain and swept over southern Italy, killing over one million people; in the Jewish Ghetto in Rome, according to Zahalon, it lasted some nine months.

When the physician visited the sick, he would hold in his hand a large tar torch, burning it night and day to purify the air for his protection, and in his mouth he had theriac . . .

“Poison antidotes figured prominently as wonder drugs, owing to their powers to cure poison alongside a wider variety of ailments. The ubiquitous theriac and its forerunner mithridatium were prime examples.”

— Alisha Rankin, The Poison Trials: Wonder Drugs, Experiment and the Battle for Authenticity in Renaissance Science. The University of Chicago Press 2021. p150.

In a recent paper on the healing properties of theriac from a group of Polish researchers, the authors explain the theory behind the use of theriac:

The humoral doctrine, based on the views attributed as far back as to Hippocrates (5th/4th c. BC), assumed the existence in body of four basic substances called the humors. Disturbance of their balance or having them spoiled would cause disease. 

The[se] humoral physicians supposed that both for epidemic and intoxication the real cause was a “venom”, entering into body and corrupting its liquids. Hence, drugs believed to neutralize poisons, such as Theriac, were used when a “venom” was diagnosed. Therefore early modern medics recommended the treacle to be used in case of epidemics (when the toxin was considered e.g. airborne) as well as after poisoning, a snake or a rabid dog bite etc.

Contemporaries actually believed that Theriac is a potent anti-epidemic drug. After all, it was used not only during the outbreaks of bubonic plague, the early modern epidemic disease par excellence. For instance, in 1551, during the sudor anglicus outbreak, numerous English physicians regarded the treacle as a staple in prophylaxis, cure and treatment of that mysterious and contagious disease. In the 17th c., London physicians assumed that Theriac might resist measles outbreaks among children and young adolescents. Whereas in German-speaking territories in the 18th c. the treacle was used as a medicine against numerous types of “typhoid fevers” and typhus, smallpox, and other contagious diseases, including the cattle plague. In Muslim world, in turn, it was widely recommended during the outbreaks of cholera.

“כי הטריאקה איננה סם אחד, אבל היא מרקחת רבת ההרכבה, יכנס בה שאור ודבש ובשר שקצים ורמשים, כי יכנסו בה אבק העקרבים ובשר האפעה, כי לכך נקראת כן, כי הארס בלשון יון תריאק. וכן בלשון תלמוד טרקיה חויא (שבת קט:), וכן הוזכרה המרקחת בלשונם כי טוריאקה לכוליה גופא (נדרים מא:), וחלילה שיכנס בקטורת בשר שקצים ורמשים ושאור

Theriac [called “triga” by Rashi] is not one ingredient but is a compound of many ingredients, containing leaven and honey, the flesh of forbidden animals and reptiles, for the powder of dried scorpions and the flesh of the viper go into it, this being the reason why it is so called [theriac], for “poison” in Greek is called theriac.

So also in the language of the Talmud:“Torkai (stung by) a serpent.” Similarly this compound is mentioned in the language [of the Rabbis]: “as theriac is good for the whole body.”’”

— Ramban, Commentary to Ex. 30:34

Fake Snake oil and Genuine Snake Oil

Over the centuries, theriac was concocted with all manner of different exotic ingredients. But how could the consumer be sure they were getting the real-deal theriac, and not some useless knock-off? Through a poison trial, obviously.

In her fascinating recent book The Poison Trials: Wonder Drugs, Experiment and the Battle for Authenticity in Renaissance Science, Alisha Rankin, a professor of history at Tufts University in Boston describes how theriac and other wonder drugs were tested. Often, a pair of criminals condemned to death would be used. They were given a poison like aconite (which comes from a genus of flowering plants which includes monkshood) and then one of them received the theriac. One such Poison Trial took place in 1524 and was overseen by the physician to Pope Clement VII. Here is Rankin:

Led by the pope’s personal physician Paolo Giovio, the doctors gave both prisoners a good quantity of a deadly aconite called napellus, enough to kill “not merely two men, but one hundred.” As the poison took effect, the prisoners started to gesticulate wildly and cry out from the pain in their hearts. Immediately, Caravitia [a surgeon who had created the antidote and offered it to the pope] anointed one of them with some of the oil, and the man’s heart and pulse quickly returned to normal. The other prisoner, who was given no antidote, died in great agony…

Less than two weeks later, a four-page pamphlet appeared in print, described as a “Testimony of the most true and admirable virtues of a composite oil against plague and all poison, with which an experiment was conducted by distinguished men, at the command of the Supreme Pontiff Pope Clement VII, in the Roman Capitoline edifice.”

Still, these trials did not convince everyone. Galen had written that “there is much trickery practiced about the drug by tricksters.” During the Renaissance period, there was concern that the theriac was inferior or outright fraudulent. The same concerns were raised about another cure-all: unicorn horn, and apothecaries had to go to great lengths to prove to the satisfaction of their customers that the horn came from a genuine unicorn.

But did it work?

It probably goes without saying, but I will say it anyway. There is nothing that we today would count as scientific evidence to suggest that theriac, in any of its recipes, actually worked. The same group of Polish researchers we cited above carefully reconstructed theriac from that the recipe of Paul Guldenius (and you can read their fascinating paper here). They concluded that “only two species included in Theriac can be harmful in humans: poppy and sea squill, but in both cases the calculated quantity of morphine and cardiac glycosides, respectively, were below toxic level.” Well at least that. And here are some more of their observations:

Summing up the results, due to the extreme complexity of the Theriac recipe after theoretical analysis it is easier to say what pharmacological effect the medicine did not have than what it actually had. Historical and phytochemical investigations have consistently shown that – at least in the Early Modern period – the assumptions regarding narcotic or toxic effects of Theriac are not supported by the results. On the other hand, taking into account the compounds one can expect positive results in antioxidant tests or antimicrobial and anti-inflammatory activity. Still, at the moment there is no indication that the famous panacea’s efficacy in the main indications was based on anything more than just a placebo effect.

This too, seems to have been understood by at least one talmudic rabbi. In reply to Rava’s statement that having a fever once every month was “as good as theriac,” his contemporary Rav Nahman bar Yitzchak had this brief retort:

לָא הִיא וְלָא תִּירְיָיקָה

- Give me neither a fever nor theriac!

Nedarim 41b ~ Fever

נדרים  מא, א–ב

אמר רבא האי אישתא אי לאו דפרוונקא דמלאכא דמותא מעלי כחיזרא לדיקלי חד לתלתין יומין

Rava said about a fever: "Were it not for the fact that it is an agent of the Angel of Death, it would be beneficial for a person as a prickly foliage is for palm trees, if it is experienced once every thirty days...(Nedarim 41a-b).

When I worked as an emergency physician I treated hundreds and hundreds of patients who came to the ER with a fever.  In fact, fever is the third most common reason in the US for which people visit the ER - accounting for over 5 million visits each year. At virtually every visit they'd be given a medicine to reduce their fever, as if by doing so we were achieving something medically important. But in this page of Talmud, we read that according to Rava, fever is actually beneficial to a person (at least when it does not kill...).  How does this claim made by Rava, a Babylonian sage who died around the year 352 CE, stand up to today's medical science? Remarkably well, it turns out. Here's why.

Fever 101

Here are some basic things to know about fever. First, it is usually defined as a core temperature in humans above 38.3 C, or 101 F.  Second, there are lots of reasons why people get a fever, of which bacterial and viral infections are the most common, but not the only causes.  Third, and this is really important, not all fevers mean the same thing in terms of their seriousness.  Fever in a baby less than a month old requires an urgent and extensive evaluation. The same fever in a healthy toddler does not.  Fever in a healthy teenager is not the same as fever in an elderly patient on chemotherapy.  Finally, fever is not caused by the infection, at least not in the way you might think. It is the body's response to that infection that produces a fever.  Here's how.

The Biochemical Pathway to Fever

When bacteria infect the body, their foreign structure is recognized by white cells in the blood called macrophages. These macrophages then release a prostaglandin E2, interleukin-1, interleukin-6, and tumor necrosis factor. These act on a region deep in the brain called the hypothalamus, which acts as a thermostat for the body. Under the influence of interleukin-1 the hypothalamus releases a hormone called cyclooxygenase 2 (COX-2) which resets the body's thermostat, causing the temperature of the body to rise by a few degrees.  

How a fever is caused by a bacterial infection. From Evans, Repasky and Fisher. Fever and the thermal regulation of immunity: the immune system feels the heat. Nature Reviews Immunology June 2015: 15: 337.

It's not just people who get fevers. Dogs and cats do too, as do mice (and all mammals), reptiles, and even goldfish. Why would so many animals respond to an infection by developing a fever?

The Benefits of Fever

The reason is simple. The immune system fights infections better when the body is hotter. The way it does this is now well-understood but very complicated; here are just the highlights. 

Under what immunologists call "thermal stress" (and the rest of us call "a fever,") neutrophils, the white cells that are needed to fight infection, are released in greater numbers from the bone marrow.  These neutrophils also do a better job of fighting bacteria at the site of the infection when the body is warmer.  Fever also improves the killing ability of another group of blood cells called natural killer cells, and it increases the ability of the macrophages to ingest and destroy the invading bacteria. In an excellent review of fever and the thermal regulation of immunity in Nature Reviews, the authors concluded that "[t]he picture that emerges is one in which febrile temperatures serve as a systemic alert system that broadly promotes immune surveillance during challenge by invading pathogens."  

So your body does a better job of fighting bacteria when it is hotter.  Why then, do doctors give medicines that reduce a fever?  Good question. The truth is, they really shouldn't.

Don't Reach for That Tylenol/Paracetomol/AcAmol 

If you are the parent of a child with a fever, you are likely to give your sick offspring a medicine that interferes with the immune system, like Tylenol if you are in the US, Paracetamol if you are in the UK or South Africa, or Acamol in Israel (though they are different words for the same medicine).  But if, as we have seen, the body does a better job of fighting infection when it is a few degrees hotter, might reducing the fever lead to a worse outcome for the child?

This question was recently examined by a group from McMaster University in Canada. They looked at the side effects of reducing a fever in those who are sick from a population level . What happens in a large group of people when some of them - infected with, say, influenza - take medicines to reduce their fever? The answer is that more of them transmit the virus and so more of them fall ill.  On a population level the effect is rather drastic:

Putting together our estimates of the treatment probability p and the individual transmission enhancement factor fi ...we conclude that the current practice of frequently treating fevers with antipyretic medication has the population-level effect of enhancing the transmission of influenza by at least 1% (95% CI: 0.04–3%)...This estimate does not take into account the known effect that the infectious period of influenza is also increased by antipyresis, nor does it take into account the potentially large effect of increasing the rate of contact among infectious and susceptible individuals because antipyresis makes infectious individuals feel better...To put our lower bound...into perspective, consider that approximately 41,400 ...deaths per year are attributed to seasonal influenza epidemics in the United States (and an order of magnitude more worldwide). Taken at face value, our results indicate, for example, that...at least 700 deaths per year ... could be prevented in the US alone by avoiding antipyretic medication for the treatment of influenza...

“In the absence of meaningful evidence for the beneficial effects of fever reduction, the commonplace reduction of fever in critically ill patients must be called into question.”

— Ryan and Levy. Clinical Review: Fever in intensive care patients. Critical Care 2003, 7:224.

The Canadian investigators concluded that "...the use of antipyretics can have subtle and potentially important negative effects at the population level. Any medical intervention that aims to relieve the symptoms of an infectious disease in an individual should also be evaluated in light of potentially harmful effects at the population level..." And it's not just populations that can suffer: individual patients are at risk too. In a 2011 paper looking at the treatment of fever in very ill patients with sepsis in the ICU,  a French team looked at the beneficial and detrimental effects of fever, and concluded that "...the widespread use of antipyretic methods in ICU patients is not supported by clinical data and fever control may be harmful, particularly when an infectious disease is progressing..."

From Lainey Y. et al. Clinical review: Fever in septic ICU patients - friend or foe? Critical Care 2011:15:222

The Death of Rav Assi - from Fever

So Rava's teaching in tomorrow's daf, Nedarim 41b appears to be spot on.  Fever is indeed beneficial for the body, though it is a sign that something bad is going on.  Elsewhere in the Talmud (Niddah 36b, which we will learn on Shabbat, May 1, 2027, הבא עלינו לטובה) we read that another Babylonian Amora, Rav Assi, died from a fever accompanied with chills - the classic description of sepsis (and a lot else besides, too). It is interesting to note that Rav Assi's attendants tried to reduce his fever.  Perhaps they were not aware of the tradition that Rava - who was born two generations later - would later teach.

R. Assi fell ill and they had to put him in hot [blankets] to relieve him from chills, and in cold [compresses] to relieve him from heat,[but] his soul departed to its eternal rest. (Niddah 36b.)

Fever may be beneficial, but the underlying infection of which it is a sign never is.  Which is why, in the next daf  (Nedarim 42), Rava's teaching was not accepted by Rav Nachman bar Yitzchak who retorted: לא היא ולא תירייקה:  "Give me neither fever, nor its antidote!"