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1,000 Year Old Remedy May Cure MRSA, Still Faces Market Hurdles

A plant-based ointment recipe pulled from a 1,000-year-old manuscript is spiking excitement about what historical knowledge and traditional remedies can do to defuse the antibiotic crisis. At the same time, it’s highlighting how difficult it can be to move any compound—natural or synthetic, ancient or modern—from the lab bench to where it might do the most good.

You might have seen coverage of this: At the annual conference of the British Society for General Microbiology last week, a team of researchers from the University of Nottingham in England and Texas Tech University in the United States presented the results of their attempt to translate and manufacture an ointment described in a medieval manuscript held at the British Library. (The abstract doesn’t seem to be online, except within the conference program, so I snipped it and uploaded it to my Scribd account here.) The text, called Bald’s Leechbook, is in Anglo-Saxon; you can think of it as one of the earliest medical textbooks written in the West. The recipe is presented as a remedy for styes, pustular infections of an eyelash follicle that, in the pre-antibiotic era—and the 10th century was definitely pre-antibiotics—could cause blindness or even death if the infection spread to the nearby brain. It specifies garlic, leek, onion, honey, and bile from the digestive system of a slaughtered cow, and describes in detail how the potion should be made, by boiling up a solution in a brass vessel and fermenting it.

And, apparently, it works. The UK arm of the team translated the recipe, concocted it, and conducted initial tests on bacteria on culture plates. The US side tested it on infected tissue harvested from lab mice. In both settings, the potion killed MRSA, drug-resistant staph—and killed at higher rates than vancomycin, a last-ditch drug that medicine reserves for serious infections with that superbug.

“We were really surprised, and I was surprised,” Christina Lee, PhD, a medieval scholar on the team, confessed by phone. “I have always held up the idea of the pragmatic Middle Ages, that they had knowledge and method, but I was not sure whether that would hold up.”

One challenge, Lee said, was figuring out just how to make the recipe. First, plants growing now are not the same as then; the team chose modern varieties, making a best guess that the chemical components would be the same. Second, the recipe—like your grandmother’s prize pound cake, maybe—contained no proportions; just a list of ingredients, and instructions to brew and hold them. The team thought maybe equal amounts would work. And last, the recipe specified a “brazen vessel”; the group settled instead for adding strips of brass copper sulfate while the potion boiled.

Initial lab tests showed the concoction killed staph, while its individual ingredients, tested separately, did not. They turned to Kendra Rumbaugh, PhD, whose lab at Texas Tech University’s Health Sciences Center frequently conducts efficacy studies of new antimicrobial compounds. She tested it using lab mice, by creating a surgical incision, infecting it with staph, killing the mice and harvesting the tissue, and then soaking the infected tissue in the medieval concoction as well as a vancomycin solution and plain saline. In the tissue treated with the medieval compound, 90 percent of the staph died.

“Whereas vancomycin did, essentially, nothing,” she told me. “Now, ideally, if you have an agent and want to go to the (Food and Drug Administration), you want to see 99.99 percent killing. We would want to see better before moving into clinical trials.”

So what happened? The researchers admit: They are not yet sure. The team includes microbiologists, but not, at this point, biochemists; as they move forward into a second phase, they hope to recruit more collaborators. “Right now, this is a crude solution with a number of ingredients,” Rumbaugh said. “They will have to figure out what the active ingredient is.”

An almost-lost medieval recipe that works is marvelous, but is it practical—or even, really, new? I checked with several biochemists, who pointed out that looking for natural antibacterials is a longstanding research endeavor. (For instance: The medieval recipe contains garlic. Here, listed at the National Library of Medicine, are 354 papers going back to the 1940s examining allicin, an antibacterial compound in garlic.)

“It is exciting that this team were able to validate an ancient traditional remedy,” said Cassandra Quave, PhD, an ethnobotanist whose Emory University lab studies the antimicrobial properties of plant compounds. “It demonstrates that traditional medicine—which 80 percent of the world still uses—isn’t just old wives’ tales, but has science behind it. But the challenge of getting anything to market is the regulatory hurdles.” Despite its plant origin, she pointed out, this remedy or anything like it probably would not be eligible for approval as a dietary supplement, for which the rules are looser. If its discoverers assert a clinical effect,  they likely would have to go to the FDA for investigational new-drug approval.

And FDA licensing requires much more detailed analysis than the researchers have done to date—essentially, taking the formula apart and then putting it back together, said David Kroll, PhD, a natural-products pharmacologist who writes the Take as Directed blog for Forbes. “What you normally do with a complex mixture is, extract out the fat-soluble and water-soluble compounds, separate the chemicals in each, and test them individually for the effect you are looking for—anti-staphylococcal activity, in this case,” he told me. “And then, if you are claiming synergy between the components, you have to put them back together, and test the results again. The mixture has to be highly defined, and highly reproducible.”

And then it has to be tested—in clinical trials, if the creators intend the compound to be licensed as an antibacterial. Complaints about the FDA’s requirements for clinical-trial design are legion (for the full story, try David Shlaes’ blog The Perfect Storm); suffice it to say that highly capitalized pharma companies already consider clinical-trial requirements a major stumbling block in creating new antibiotics.

Quave and Kroll pointed out that 10 years ago, the FDA approved an accelerated, streamlined approval process for plant-based products, called the Botanical Drug Pathway. In the decade since, according to the blog Fierce Pharma, it has received more than 500 applications for plant-based medications—and approved two.

The tentative conclusion for now: In retrieving this almost-lost remedy from antiquity, the team that produced and tested this crude but fascinating medication faced significant challenges. But the hurdles they will have to leap, if they attempt to move it forward into a viable product, will be higher yet.

 

 

16 thoughts on “1,000 Year Old Remedy May Cure MRSA, Still Faces Market Hurdles

  1. The article says “But the challenge of getting anything to market is the regulatory hurdles.” So I wish the headline had said

    “1,000 Year Old Remedy May Cure MRSA, Still Faces Regulatory Hurdles”

    MM: Sadly, that has more characters than our style allows! But yes, I take your point.

  2. Question: I assume the diet of cows at the time this was written was only grass. Cows raised on CAFOS today cannot fight off their on infections because of their corn based diet and antibiotic regimen. Would this remedy work with bile from just any slaughtered cow today?

  3. My instinct would be to test for copper and zinc compounds first, as an alloy of the two metals is known to kill MRSA. After 9 days fermentation there is probably going to be a wide range of acids and potential ligands.

  4. SEE, SEE, SEE. We don’t need tons of chemicals that weaken our body after treatment and no mercury in our bodies because that just destorys our neurolocgical pathways in our brains and nerves. Herbical and natural treatments are way safer and they don’t damage our bodies after treatment like todays’ ‘medicine’. I find that using non-chemical concoctions that are not made up of harmfull elements that destory not only the virus or bacteria, but also our bodies as well, are safer to use.

    1. How do you back up the assertion that the ointment is not “chemical”? Since they have not figured out how the ointment works, it could be any number of chemicals that are the active ingredient, and it could be that it is a “chemical” that is produced from the chemical reaction of certain ingredients in the ointment. Isn’t that chemistry?

      Many chemicals in use today are plant derivatives, do you still count those as chemicals? What about taking vitamins vs. eating nutrient rich foods, are those vitamins also chemicals?

  5. This article is extremely interesting. Researchers in Poland have found that by using a combination of plant extracts and silver nanoparticles they can kill 99.9% of MSRA without causing any damage to human tissues. Amazing, what medicine can learn if the chemicals are put away.

  6. http://articles.economictimes.indiatimes.com/2011-05-24/news/29577655_1_superbugs-antibiotic-resistant-bacteria-cockroach

    Simon Lee, a co-researcher from the School of Veterinary Medicine and Science at Nottingham University, says their study suggests that many molecules inside the cockroach brain have favourable physico-chemical characteristics and would make good candidates for drugs suitable for use in humans; the research is funded by the University of Nottingham, the UK Ministry of Defence, and the Aga Khan University.

    Khan adds that though their study is at an early stage, “preliminary work suggests that these molecules (in the cockroach’s brain) are proteins in nature a¦ we have found nine molecules which have potent activity against multi-drug resistant bacteria”.

    The researchers expect to bring antibiotics sourced from the cockroach’s brain to a pharmacy near you in the next 5-10 years.
    http://aem.asm.org/content/77/16/5794
    Centre for Genetics and Genomics, School of Biology, University of Nottingham, Medical School, Queen’s Medical Centre, Nottingham
    Bdellovibrio orally administered to birds that had been predosed with a gut-colonizing Salmonella enterica serovar Enteritidis phage type 4 strain (an important zoonotic pathogen) significantly reduced Salmonella numbers in bird gut cecal contents and reduced abnormal cecal morphology, indicating reduced cecal inflammation, compared to the ceca of the untreated controls or a nonpredatory ΔpilA strain, suggesting that these effects were due to predatory action. This work is a first step to applying Bdellovibrio therapeutically for other animal, and possibly human, infections.

  7. I am just wondering what the approval process was for coal tar by FDA

    According to the National Psoriasis Foundation and the FDA, coal tar is a valuable, safe and inexpensive treatment option for millions of people with psoriasis and other scalp or skin conditions.[13] Coal tar concentrations between 0.5% and 5% are safe[who?] and effective for psoriasis, and no scientific evidence suggests that the coal tar in the concentrations seen in non-prescription treatments is (or is not) carcinogenic because there are too few studies and insufficient data to make a judgement. Coal tar contains approximately 10,000 chemicals, of which only about 50% have been identified,[14] and the composition of coal tar varies with its origin and type of coal (for example,: lignite, bituminous or anthracite) used to make it.

  8. The FDA, in my opinion, is a criminal organization. The revolving door relationship between big pharma executives and the FDA is shameful. They are alright with rushing harmful drugs to the market, drugs that wind up killing the end user while rejecting potentially life saving drugs. It’s a blatant conflict of interest yet it has continued for decades. Why in the hell does the FDA need armed men and swat teams who raid people for buying or producing raw milk while big corporations poison thousands of people every year with their unsanitary and disgusting practices? In the end it’s about the money, not the people.

    1. Your view is exactly correct. FDA is an abomination to the world of science and innovation…a self-serving cabal that protects Pharma not the health of the people.
      Thank you Grey.

  9. http://www.bbc.com/news/health-32551873

    C. diff used to beat C. diff infection
    C. difficile infections cause diarrhoea and fever.
    They have been a major problem in hospitals around the world, with around 29,000 deaths in the US alone linked to the bug each year.
    Should I have posted this under Polio ?
    The symptoms are caused by toxins released by C. difficile bacteria.
    So the team at Loyola University Health System in Illinois tried giving patients spores of non-toxin-producing C. difficile.
    The friendlier bacteria should occupy the spaces in the gut that the toxic C. difficile normally inhabits and prevent it coming back.
    The trial showed the healthier bacteria took hold in the gut 69% of the time. In those people, just one in fifty faced another infection.
    Meanwhile, one in three people had renewed symptoms if the bacteria failed to colonise the gut or if they were given a dummy treatment.
    Dr Dale Gerding, one of the researchers at Loyola University Health System, told the BBC: “C. difficile infections are the most common hospital-acquired infection that we have, it is a big problem.
    Dr Simon Clarke, from the University of Reading, told the BBC: “It is an interesting idea, it is a less grim version of a faecal transplant and a very interesting concept to block infection.
    “They are still infected with bacteria, but they are a more friendly version.
    “This paper established the proof of principle, but what they need to do is find out exactly how you can use it.”

  10. I’m glad to see I’m not the only one who sees the truth. “The FDA, in my opinion, is a criminal organization. The revolving door relationship between big pharma executives and the FDA is shameful. They are alright with rushing harmful drugs to the market, drugs that wind up killing the end user while rejecting potentially life saving drugs. It’s a blatant conflict of interest yet it has continued for decades. Why in the hell does the FDA need armed men and swat teams who raid people for buying or producing raw milk while big corporations poison thousands of people every year with their unsanitary and disgusting practices? In the end it’s about the money, not the people.”

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