Shabbat 108-110 ~ Might Talmudic Medicines Really Work?

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For the next couple of days, those who study the Talmud following the one-page-a-day Daf Yomi cycle will spend some time reading about cutting edge medical practices.  In Babylon. About 1,500 years ago. Here's a smattering of some of those practices:

For  a hand or foot wound

  • Immerse the wound in wine (especially if you are from Mehoza). For injuries to the back of the hand, use vinegar instead (Shabbat 108b).

For liver worms

  • Swallow some white cress. If that does not help, you should fast, and then take fatty meat and place it on coals and suck the bone and swallow vinegar. If that does not help, take the sawdust that was scraped from the shell of a thorn bush from top to bottom, (though not from bottom to top, since perhaps then the worms will come out through the mouth). Then boil the scrapings in beer at twilight and the next day close your nostrils and drink it. Then defecate on the trunk of a palm tree (Shabbat 109b).

For a snake bite

  • Tear up the fetus of a white donkey. Apply to the wound (Shabbat 109b).

For a genital discharge

  • Boil three pans of Persian onions in wine. Drink the mixture (Shabbat 110b). If the discharge persists, take a fistful of cumin, saffron, and fenugreek, cook them in wine, and give drink, while saying to the patient: “Stop emitting your discharge” (Shabbat 110b).

For jaundice

  • Drink grasshopper brine. If your chemist lacks grasshopper brine, substitute with brine of small birds, enter a bathhouse, and smear yourself (Shabbat110b).

For toothache

  • Swish with wine vinegar (Shabbat 111a).

We could go on but no doubt you've got the idea.  While I doubt there are many of us eager to look for a pregnant white donkey should we be bitten by a snake, some ancient remedies appear to have remarkable healing properties. Here, for example is a review of the healing properties of acetic acid, better known as vinegar, which today’s page of Talmud recommends for a number of different conditions. It was published in a paper earlier this year.

Vinegar is generally acknowledged to act as a mild disinfectant, and pure acetic acid has been shown to exhibit various bactericidal effects at concentrations similar to or lower than those typically found in vinegar. This includes the ability to kill cells of key opportunistic pathogens living as monospecies biofilms (clinical isolates of the Gram-negative species Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis, plus the Gram-positive species Staphylococcus aureus. As a weak acid, it can readily cross cell membranes and collapse the cross-membrane proton gradient necessary for ATP synthesis; once inside the cell, acetic acid alters the cytoplasmic pH, and this can cause DNA damage and protein unfolding. A clinical trial into the effectiveness of acetic acid for treating burn wound infections is under way in the United Kingdom.

A rich source of new antimicrobials potentially resides in medieval and early modern medical texts
— Harrison F, Roberts AEL, Gabrilska R, Rumbaugh KP, Lee C, Diggle SP. 2015. A 1,000-year-old antimicrobial remedy with antistaphylococcal activity. mBio 6(4):e01129- 15.

A 1,000-Year-Old Antimicrobial Remedy

Bald’s eyesalve. A facsimile of the recipe, taken from the manuscript known as Bald’s Leechbook (London, British Library, Royal 12, D xvii).

Bald’s eyesalve. A facsimile of the recipe, taken from the manuscript known as Bald’s Leechbook (London, British Library, Royal 12, D xvii).

I am not aware of any published descriptions of attempts to test these talmudic remedies. But a recent paper described something close. It was an attempt to reproduce a remedy described in Bald's Leechbook, an English medical text written in the tenth century. This text, which exists as a single copy in the British Library in London, contains a number of remedies, including those for what appear to be microbial infections.  Here's one of them:  

Make an eyesalve against a wen [a lump in the eye]: take equal amounts of cropleac [an Allium species] and garlic, pound well together, take equal amounts of wine and oxgall, mix with the alliums, put this in a brass vessel, let [the mixture] stand for nine nights in the brass vessel, wring through a cloth and clarify well, put in a horn and at night apply to the eye with a feather; the best medicine.

Image of a hordeolum.jpeg

The most likely clinical condition that correlates with a wen is a hordeolum, or, in non-medical language, a sty. It's a bacterial infection of an eyelash follicle, caused by a common bacterium called Staph. Aureus. They are easily treated with antibiotic cream and warm compresses. A group of medical researchers (with the help of a historian from the School of English and Centre for the Study of the Viking Age at the University of Nottingham) tested the effect of Bald’s eyesalve on Staph. aureus. They wanted to to determine if it worked at all.  If it did, they wanted to see if its efficacy could be attributed to a single ingredient, or whether it only worked when all the ingredients were combined according to the instructions laid down by Bald.  

Of course the first thing the scientists needed to do was to figure out what some of ingredients were. For example, copleac might be an onion, or a leek. (Actually, they couldn't figure out which of the two it was, so they made two variants of the recipe.) Next, they took both the recipe, and controls, which were the individual ingredients alone, and after leaving them to stand for "nine nights" as the Leechbook requires (læt standan ni􏰍on niht) they applied them to colonies of Staph Aureus. Then they counted the number of colonies of the bacteria that remained.

Two hundred microliters of ES-Onion or ES-Leek (batch A, filled circles, and batch B, open circles) or of each individual ingredient preparation was added to five 1-day-old cultures of S. aureus growing at 37°C in a synthetic wound. After 24 h of fu…

Two hundred microliters of ES-Onion or ES-Leek (batch A, filled circles, and batch B, open circles) or of each individual ingredient preparation was added to five 1-day-old cultures of S. aureus growing at 37°C in a synthetic wound. After 24 h of further incubation, the collagen was dissolved to recover cells for agar plate counts. The control treatment was sterile distilled water left to stand for 9 days in the presence of brass, which was also present in all other preparations, to simulate the presence of a copper alloy vessel Asterisks denote treatments whose results were significantly different from those of the control. From Harrison F, Roberts AEL, Gabrilska R, Rumbaugh KP, Lee C, Diggle SP. 2015. A 1,000-year-old antimicrobial remedy with antistaphylococcal activity. mBio 6(4):e01129-15.

To their great delight they found the recipe was only effective when all the ingredients were present. They even tested whether it was necessary to wait for nine days and reported that "the number of viable cells left after treatment with either version...was [significantly] lower when the eyesalve had been left to stand for 9 days prior to use." In other words, the potion concocted only worked when the recipe was followed in its entirety; skipping any part decreased the efficacy.    

What is the remedy for a boil? — Abaye said: [A mixture of] ginger and silver dross and sulphur and vinegar of wine and olive oil and white naphtha laid on with a goose’s quill.
— Gittin 86a

But the next experiments were no less remarkable. The researchers tested the potion on methicillin-resistant Staph. Aureus (MRSA) which is an entirely modern "superbug". Through the indiscriminate and widespread use of antiobiotics, this strain of Staph. Aureus has grown resistant to the usual antibiotics, and is very real health problem.  The researchers tested the onion (ES-O) and leek (ES-L) versions against a standard antibiotic used to treat MRSA, called vancomycin, using mice that had been infected with the superbug. Vancomycin, the standard modern therapy, did not cause significant reductions in viable bacteria, but "ES-O and ES-L caused statistically significant drops in the numbers of viable cells recovered from wounds." In fact when compared to our modern vancomycis, the Leechbook potions caused a ten-fold reduction in the number of viable MRSA cells recovered. Of course there's a long way between a single small study done on cell cultures and mice, and a drug that is safe and effective in humans. But this story reveals how come very old medical texts may contain treatments that work, and another analysis of an old Welsh medical text published in the Journal of Ethnopharmacology also found several ingredients with antimicrobial activity.

[For more on the the story of the discovery of Bald'eye remedy, listen to this wonderful podcast:]

Data Mining a Medieval Medical Text

Earlier this year a group of scientists took the Bald’s Leechbook idea to the next level. Perhaps medieval medical texts could be turned into electronic databases which could then be explored by a computer algorithm. This time the text was the 15th-century Lylye of Medicynes, which focuses on remedies to treat symptoms of microbial infection. (The book is a Middle English translation of Bernard of Gordon’s Lilium Medicinae, originally completed in the early 14th century. The text is extant in one manuscript, University of Oxford, Bodleian Library, MS. Ashmole 1505.)

The book has an amazing 3,548 ingredients (747 unique names) used to treat 124 unique disease names, of which 41 could be classified as potential skin, mouth, or eye infections. Then the team looked to see which ingredients were commonly used together, and built patterns of ingredients, like this:

Example of an ingredient network. The nodes in yellow are ingredients of a recipe for the treatment of fistula in lacrimali; those in blue are ingredients of a recipe for the treatment of pascionibus oris. Ingredients found in both recipes are color…

Example of an ingredient network. The nodes in yellow are ingredients of a recipe for the treatment of fistula in lacrimali; those in blue are ingredients of a recipe for the treatment of pascionibus oris. Ingredients found in both recipes are colored both yellow and blue. Thicker links join pairs of ingredients that appear in both recipes.

In this way the group could identify which ingredients were core components. These were then tested for activity against two Gram-positive opportunistic soft tissue pathogens (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative opportunistic soft tissue pathogens (Escherichia coli and Pseudomonas aeruginosa).

Antimicrobial activity.jpg

As you can see in the table above, there are some interesting results. The combination of Aloe vera and breast milk could interfere with the killing effects of honey (for P. aeruginosa and E. coli) or those of frankincense plus sumac (for P. aeruginosaE. coli and S. aureus); however, in the case of E. faecalis, combining bile with honey or combining frankincense-sumac with honey led to the synergistic emergence of bactericidal activity.

Perhaps, noted the authors, “the combinations of honey, acetic acid, bile, and frankincense and/or sumac may be worth investigation for their ability to potentiate each other’s antibacterial effects…”

If medieval physicians really did use observation and experience to design effective antimicrobial
medicines, then this predates the generally accepted date for the adoption of a rational scientific method (the formation of the Royal Society in the mid-17th century) and the modern age of antibacterial medicine (Lister’s use of carbolic acid in the late 19th century) by several hundred years.
— Harrison F, Roberts AEL, Gabrilska R, Rumbaugh KP, Lee C, Diggle SP. 2015. A 1,000-year-old antimicrobial remedy with antistaphylococcal activity. mBio 6(4):e01129-15

The 2015 Nobel Prize for an Ancient Remedy

...take one bunch of Qinghao, soak in two sheng of water, wring it out to obtain the juice and ingest it in its entirety
— Extract from The Handbook of Prescriptions for Emergency Treatments by Ge Hong (283–343 CE).

Another example of the medical wisdom of some ancient texts was acknowledged by the Nobel Prize Committee, no less. In 2015, the Nobel Prize in Medicine was shared by the Chinese physician Youyou Tu "for her discoveries concerning a novel therapy against Malaria." Professor Tu led a team that screened more than 2,000 traditional Chinese medical herbs for antimalarial activity. Extracts from a herb known locally as Qinghao, (Artemisia annua) inhibited the malarial parasite and was successfully tested on mice in 1971. Clinical studies in the 1980s established the efficacy of artemicinin (as it came to be called). This drug is now part of the standard treatment for malaria worldwide.  Yet it was first identified in a Chinese medical text from the third century CE. - the era of the Mishnah and early Talmud.

But do be careful…

Ancient texts certainly may contain efficacious treatment, though the odds are stacked against them. Today only a very tiny number of compounds that are screened for possible medical benefit ever make it to early trials, and of those most fail. It would take a lot of convincing to get Pfizer to test a "woodcock with its throat cut with a coin" for headache.  Until then, it is best to follow the words of another very old source of wisdom, Rav Sherira Gaon, who died around the year 1000 CE. (and so lived around the time of the composition of Bald's Leechbook). 

אוצר הגאונים, חלק התשובות, גיטין דף ס"ח ע"ב, סימן שע

צריכין אנן למימר לכון, דרבנן לאו אסותא אינון, ומילין בעלמא דחזונין בזמניהון...אמרונין, ולאו דברי מצוה אינון. הלכך לא תסמכון על אלין אסותא, וליכא דעביד מינהון מידעם, אלא בתר דמיבדיק וידע בודאי מחמת רופאים בקיאים, דההיא מילתא לא מעיקא לה וליכא דליתיה נפשיה לידי סכנה. והכין אגמרו יתנא ואמרו לנא אבות וסבי דילנא, דלא למעבד מן אילין אסותא אלא מאי דאיתיה

We must tell you that the rabbis were not physicians. Whatever they saw in their day, they addressed, but these matters are not mitzvot. Therefore, do not rely on these remedies. They must not be applied until they have been tested by expert physicians, who can be sure that the remedy will not cause harm or danger. This is what our ancestors have taught us. We should not apply these remedies unless they have been tested...

[A largely updated post originally published here.]

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