The Survival Cabinet: Penicillin, Garlic, Honey & The Long War Against Infection - Episode 17

00:00:00: I want you to think about the last time you took an antibiotic.

00:00:03: Maybe it was recently, maybe it was years ago.

00:00:06: A course of tablets probably twice a day with food finished whole pack Something that felt unremarkable routine The kind thing you do and then forget.

00:00:15: Now i want you thinking what tablet is actually doing in your body.

00:00:19: It was borrowing a weapon from a fungus.

00:00:22: Specifically, it was deploying a chemical that a mold evolved millions of years ago to kill the bacteria competing with it for food!

00:00:29: That chemical-refined concentrated synthesized in a pharmaceutical facility was now running through your bloodstream targeting bacteria by the same mechanism it evolved to use in soil.

00:00:40: You were –in most literal sense– borrowing weapons that has been going on in the earth beneath our feet since long before humans existed.

00:00:50: And here is a thing I find humbling about this, people were using versions of these weapons thousands years ago when anyone understood what it was or how they worked.

00:01:00: Egyptian physicians were packing wounds with moldy bread and Anglo-Saxon healers made garlic and onion preparations.

00:01:06: modern scientists have tested against most resistant bacteria we had found to be effective.

00:01:12: Honey has been used as a wound dressing continuously for over four thousand years and modern medicine has verified in molecular detail why it works.

00:01:21: The survival cabinet, the collection of things humans have use to fight infection throughout history did not begin at the twentieth century laboratory – It began in kitchen, garden & accumulated painstaking empirical observation on what works And when its finally arrived told us why it worked.

00:01:38: Today we are going to go both places, the kitchen and laboratory.

00:01:42: The ancient remedy and modern drug And were gonna meet some remarkable people along the way including a woman in Illinois who went shopping for moldy fruit and changed history of medicine A policeman whose story has been told wrong for eighty years.

00:01:57: I'm Alexandra Welcome To The Hidden Life Of Things Everyday History.

00:02:00: For Anyone Who's Ever Looked At Something Originary How Did This Actually Get Here?

00:02:06: To understand why penicillin changed everything, you need to feel what the world was like before.

00:02:11: And a way of feeling that is think about small things not plague or cholera and not great epidemic diseases killed millions at one time.

00:02:19: Small things The ordinary injuries of ordinary life A scratch cut from kitchen knife A tooth ached and infected A child who grazed their knee and skin turned red around.

00:02:29: wound Red is still then began to swell A soldier with a wound that seemed clean at first and then, few days later unmistakably wasn't.

00:02:37: Before antibiotics.

00:02:38: those small things killed people Not always not even usually for most people with healthy immune systems And reasonably clean environments But regularly With the frequency modern people find difficult to fully imagine Because our baseline has shifted so completely.

00:02:53: Cepsis Blood poisoning The condition where bacteria enter bloodstream and trigger system-wide inflammatory response killed healthy adults in days.

00:03:02: Child bed fever killed women who had just given birth and maternity wards across Europe until a Hungarian physician named Ignas Semmelweis worked out, In the eighteen forties that doctors were transmitting it on their unwashed hands between patients.

00:03:16: A discovery so threatening to medical dignity That The profession largely ignored It.

00:03:21: And Semmelwise died at a mental institution Possibly from the very infection he had spent his career trying to prevent.

00:03:27: Surgical infection killed patients who had survived the injury itself.

00:03:31: A burst appendix and infected wisdom tooth pneumonia, any of these could be death

00:03:35: sentences.".

00:03:36: The average life expectancy in England in nineteen hundred was around forty-seven years by nineteen fifty.

00:03:41: after the widespread introduction of antibiotics on other public health measures it had risen to around sixty.

00:03:47: nine years.

00:03:48: this is over twenty years added to an average human life in half a century.

00:03:52: New single technological development in human history has extended human life by as much the control of bacterial infection.

00:03:59: And this story about how we got there is not a clean, triumphant narrative that gets told on textbooks.

00:04:04: It's messier, stranger more distributed and more dependent upon people whose names most have never heard Here.

00:04:11: something I think one important idea for you all.

00:04:15: The people who used multi bread on wounds Who packed garlic into infected cuts Who dressed burns with honey Those people were not primitive, they weren't ignorant.

00:04:24: They're doing something that is genuinely scientific in its method even if it's not vocabulary.

00:04:29: They were observing and testing what worked.

00:04:33: to pass on the knowledge.

00:04:36: In ancient Egypt physicians used multi-breads as topical treatments for infected goons from at least fifteen fifty BCE.

00:04:45: We know this from medical papyri.

00:04:47: They didn't know what molds were.

00:04:48: They had no concept of bacteria, but they noticed carefully and repeatedly across generations that wounds treated this way did better than wounds that weren't.

00:04:58: The empirical observation was correct the mechanism invisible to them.

00:05:01: But the outcome is real.

00:05:03: Ancient Greek physicians made similar observations, sorted physicians in ancient China India And across the Middle East.

00:05:09: The pattern appears too many independent traditions To be coincidence.

00:05:13: It's the accumulated result of millennia Of human beings paying careful attention to what happened when they tried different things on infected wounds.

00:05:21: And then there is Bald's Eye Salve, a thousand-year old remedy from an Anglo-Saxon medical text called Bald's Leech Book probably compiled in the ninth century CE contains a recipe for treating eye infections that involves garlic, leek or onion wine and ox bile brewed together in a copper vessel left to stand nine days before use.

00:05:41: In twenty fifteen a team of researchers at The University of Nottingham decided test this recipe not to demonstrate that it was useless, but genuinely test whether worked.

00:05:51: They made the preparation exactly as specified in original text.

00:05:55: They tested it against Staphylococcus aureus biofilms, including MRSA.

00:06:00: The antibiotic-resistant superbug that is one of the most feared pathogens in modern hospitals.

00:06:05: Baal's eye salve destroyed up to ninety percent of the MRSA bacteria in the biofilm.

00:06:10: A thousand year old recipe written by a physician who had no concept of bacterial germs or infection as we understand was more effective against One Of The Most Dangerous Drug-Resistant Bacteria We Know Of than many modern treatments Because the Anglo-Saxon Healer had been paying attention, had noticed what worked and had written it down.

00:06:29: The knowledge was there hidden in plain sight on a manuscript that most people assumed to have met evil superstition until someone bothered to actually test it.

00:06:38: Let me explain garlic properly because I think most people know its supposed be healthy without quite understanding why And actual mechanism is much more interesting than general idea.

00:06:48: Garlic contains two things which live in separate compartments within the clove.

00:06:53: One is a compound called alan.

00:06:55: The other an enzyme called alanase.

00:06:57: As long as the clove is intact, unbroken and damaged these two substances don't meet.

00:07:02: They stay in their separate cellular compartments inert doing nothing.

00:07:06: Now why would our plant evolve this arrangement?

00:07:08: Because garlic isn't making medicine for us.

00:07:11: it's making a defence system For itself.

00:07:13: When a pest bites into a garlic clove A soil insect or fungus or bacterium trying to eat the bulb it ruptures those compartments, the alan and the alanase neat.

00:07:23: They react instantly producing a third compound called allicin.

00:07:27: Allicin is the chemical that gives crushed garlic its characteristic pungent smell And it tears.

00:07:32: in context of microbiology are highly effective antimicrobial agents.

00:07:37: It penetrates bacterial cell membranes and disrupts enzymes.

00:07:40: bacteria need to carry out essential metabolic processes.

00:07:43: It kills them or prevents them from reproducing by essentially jamming their internal machinery.

00:07:49: The important thing to understand is this, allicin is only produced when the garlic is damaged.

00:07:54: An intact clove of garlic has no allicine in it!

00:07:56: When you crush it your trigger a reaction that creates it.

00:07:59: This is why Garlic must be crushed or chopped and used relatively quickly because Allicin Is chemically unstable And breaks down within hours To have its antimicrobial effect.

00:08:09: Cooking garlic destroys the alanase enzyme before it can do its job which is why cooked garlic tastes different and lacks the antibiotic properties of raw garlic.

00:08:18: The full wisdom – eat raw garlic for its medicinal properties, it's chemically accurate!

00:08:23: But people who developed this knowledge over centuries of observation were correct even without any understanding of allicin or enzymes or bacterial cell membranes.

00:08:33: Honey is a more complicated story.

00:08:35: in some ways are more remarkable one.

00:08:40: There are pots of honey found in Egyptian tombs over three thousand years old that still technically edible.

00:08:46: Not appetizing by modern standards perhaps, but not dangerous and decomposed – Still Honey!

00:08:52: The reason honey doesn't spoil is the reason it works as an antimicrobial agent And operates through several mechanisms simultaneously.

00:09:00: The first is osmosis.

00:09:01: Honey has a extraordinarily high sugar concentration and very low water content typically below twenty percent water.

00:09:08: When bacteria comes into contact with honey, the sugar concentration gradient pulls water out of bacterial cells by osmosis.

00:09:16: The bacteria essentially dehydrate – they shrivel and die!

00:09:19: The second mechanism is more elegant.

00:09:21: Honey contains an enzyme called glucose oxidase produced by bees that make it Under normal conditions in a sealed jar away from moisture.

00:09:30: This enzyme is dormant.

00:09:31: But when honey is applied to a wound and comes into contact with the slightly diluted, slightly more alkaline environment of body fluids The enzyme activates.

00:09:40: It begins to slowly convert the glucose in the honey-into-gluconic acid In hydrogen peroxide.

00:09:46: Hydrogen peroxide is a disinfectant –the same substance–in much more concentrated form that you might use to clean a cut!

00:09:53: In Honey it's produced in small sustained amounts Enough to kill bacteria without being concentrated enough with damaged, healthy tissue.

00:10:01: It is a slow-release self regulating antiseptic.

00:10:04: Medical grade honey specifically manuka honey from New Zealand produced form the flowers of Manuka tree Is now an approved wound dressing in hospitals across Europe and United States.

00:10:15: it's used on burns, chronic wounds or surgical sites that resist conventional treatment.

00:10:20: The NHS uses it.

00:10:22: US military has use it combat trauma care.

00:10:25: Four thousand years of empirical observation validated by modern molecular biology now sitting in a hospital-worn care kit.

00:10:32: That continuity is remarkable!

00:10:35: Now we get to the story most people think they know, and as with most stories people think that they know their reality's.

00:10:40: more interesting than version gets told.

00:10:42: In September nineteen twenty eight Alexander Fleming returned to his laboratory at St Mary's Hospital in London.

00:10:48: after holiday He had been studying Staphylococcus bacteria, a common cause of wound infections and left some petri dishes unsealed before he left.

00:10:57: When he came back one of the dishes became contaminated with moulds.

00:11:02: around them there was clear zone Aeloh of dead Bacteria.

00:11:06: The mould produced something that killed it.

00:11:10: Fleming identified the mould as belonging to Penicillium genus.

00:11:14: He named the substance it was producing.

00:11:16: penicillin And this is the part that the standard story usually glosses over, he essentially moved on.

00:11:24: Fleming was a bacteriologist – not chemist!

00:11:27: He recognized what he had found but couldn't stabilize or purify active compounds in form useful as drugs.

00:11:34: The mold broth produced very limited potency and tried some surface infections with limited success.

00:11:40: He could get it to work systematically injected into his body where it would be needed.

00:11:48: He concluded that it might have some limited topical use and largely set the problem aside.

00:11:54: For nearly a decade, penicillin was essentially a laboratory curiosity.

00:11:58: Fleming's nineteen twenty-nine paper was read, noted and not followed up at any significant scale.

00:12:03: The revival came in Oxford in nineteen thirty nine when an Australian pathologist named Howard Flory And German Jewish biochemist named Ernst Chien who had fled to Britain to escape Nazis decided to investigate naturally occurring antimicrobial substances.

00:12:18: They came across Fleming's paper, they began working on penicillin!

00:12:22: What Florian Chain did that Fleming had not was bring the full resources of biochemistry through a problem – they worked out how to purify and concentrate penicilin from the mold broth.

00:12:33: They tested it on mice infected with lethal dorsus of steptococcus?

00:12:37: The treated mice survived…the untreated mice died...The results were unambiguous.

00:12:42: Now they needed to test it in a human.

00:12:45: In February, nineteen forty-one, A forty three year old Oxford policeman named Albert Alexander was dying in the Radcliffe infirmary.

00:12:52: He had developed a severe infection that has spread throughout his face and body.

00:12:56: he had already lost one eye.

00:12:58: His face was covered in abscesses.

00:12:59: an infection had spread to his lungs.

00:13:02: Every available treatment have been tried.

00:13:04: He was deteriorating.

00:13:05: Flory's team decided Alexander was a candidate for their experimental drug.

00:13:10: On the twelfth of February, nineteen forty-one he was injected with penicillin.

00:13:14: Within twenty four hours He began to improve.

00:13:17: The fever dropped and abscesses started to recede.

00:13:20: His doctors described it as a miraculous recovery.

00:13:23: A man who had been dazed from death Was getting better And then the penicilin ran out.

00:13:29: Flores' team had so little of the drug that they resorted to collecting Alexander's urine every day, cycling it back into a laboratory and re-extracting the penicillin his kidneys were excreting to reuse.

00:13:41: Even recycling this way couldn't produce enough – then fiction returned.

00:13:45: Albert Alexander died on the fifteenth of March, nineteen forty one.

00:13:50: Now here is the detail most accounts get wrong.

00:13:52: Most tellings describe Alexander's original wound as a scratch from a rose bush in his garden.

00:13:58: It is good story, peaceful and a man gardening, a thorn an infection of the most ordinary domestic accident

00:14:04: imaginable.".

00:14:05: It was almost certainly not true!

00:14:07: A twenty-ten interview with a medical historian named Eric Seidbottom and later confirmation by Alexander's own daughter Sheila who still alive living California gave different account.

00:14:18: Albert Alexander was likely wounded during a German bombing raid, shrapnel from a bomb that hit his police station.

00:14:24: His daughter confirmed this noting the Rosebus story is probably wartime propaganda designed to make medical drama more palatable and less military sensitive.

00:14:33: So The first human to be treated with penicillin Was probably man-wounded in Blitz Not a man pruning roses!

00:14:38: The wound came form a bomb not a thorn And doctors who treated him recycled urine To extract enough of drug to keep him alive for few weeks.

00:14:47: History is messier than the versions that get told, and usually more interesting.

00:14:51: Albert Alexander's death was not the end of The Penicillin story.

00:14:54: it was proof-of concept made everything urgent.

00:14:57: The problem was scale.

00:14:59: Florian chain could produce enough penicillins for mice and barely enough one human patient using bedpans or milk turns in bookshelves lined with shallow cultural vessels To produce enough to treat patients at any scale let alone supply a wartime army.

00:15:13: they needed completely different approach.

00:15:16: In nineteen forty-one, Flory traveled to the United States to seek help.

00:15:20: He ended up at the USDA laboratory in Illinois which had expertise on industrial fermentation.

00:15:25: specifically they have been working with deep tank fermentation methods that could in theory produce penicillin at a completely different scale from surface growth method Flory has used in Oxford.

00:15:37: The team took on challenge and immediately hit fundamental problem.

00:15:41: Fleming's original mold strains simply didn't produce enough penicillin.

00:15:45: Even in optimal conditions, it was too low yielding to support mass production.

00:15:50: so they began searching for better strains.

00:15:52: They sent requests.

00:15:53: laboratories around the world collect mold samples any mold samples test them for penicilin yield .They tested hundreds of strains from across the globe and The best one they found was in a fruit market In Illinois.

00:16:06: Here is where the story gets slightly historically complicated And I want to be honest about that.

00:16:11: A woman named Mary Hunt, a bacteriologist at the laboratory who had been assigned the task of scouring local markets for interesting mold samples and whom became known as Moldy-Mary is often credited with finding the cantaloupe.

00:16:24: But some accounts including one from Kenneth Rapeurr ,one of the lead researchers in the lab suggested may have been an anonymous housewife whose simply handed her moldy cantaloup to a guard at their laboratory entrance and walked away without leaving her name.

00:16:38: Whether it was Mary Hunt or an unnamed woman on the fruit market What is certain in this?

00:16:42: A moldy cantaloupe from a market turned out to carry a strain of penicillium rubens that produced initially around two hundred times more penicilin than Fleming's original strain.

00:16:54: After further enhancement through X-ray mutation and filtration, techniques applied the mold itself to encourage more productive variants – the yield reached approximately one thousand times Fleming' s originals!

00:17:07: That is what made mass production possible.

00:17:09: Not the chemistry, not the fermentation equipment or moldy cantaloupe either from a careful scientist who knew what she was looking for but from her housewife who noticed something interesting and handed it on her way past The mold strain of that cantaloup.

00:17:23: Penicillium.

00:17:24: Rubens is still used to manufacture penicillin.

00:17:26: today.

00:17:27: Every course of amoxicilline every penicilin injection given in hospital anywhere in world is produced by descendants in that one market, in Illinois.

00:17:38: In the summer of nineteen

00:17:39: forty-three.".

00:17:40: That is one of most extraordinary single facts I have ever encountered when researching this podcast.

00:17:46: By nineteen forty four penicillin was being produced in sufficient quantities to supply allied forces.

00:17:51: It's estimated that Penicillins saved over twelve percent of soldiers who would otherwise had died from infected wounds during World War II.

00:17:58: A number translated into actual people runs through hundreds and thousands.

00:18:04: After the war, a golden age of antibiotics began.

00:18:06: New classes were discovered in rapid succession, streptomycin, chloramphenicol, tetracycline and erythromycin.

00:18:15: The pharmaceutical industry poured resources into antibiotic discovery.

00:18:18: by the nineteen sixties and seventies there was genuine widespread belief that bacterial infection had been essentially concrete.

00:18:26: That antibiotics are permanent victory over nature.

00:18:29: This belief led to practices that we now understand were catastrophic.

00:18:32: Antibiotics were prescribed liberally for viral infections they couldn't treat, for minor conditions which would have resolved without them as a precaution when the precaution wasn't needed.

00:18:44: In agriculture antibiotics are fed to livestock not to treat disease but promote growth –a practice that exposed billions of bacterial cells in low-level antibiotic concentrations during extended periods.

00:18:55: And bacteria evolved!

00:18:56: Bacteria reproduced in minutes, expose billions of them to a substance that kills most but not all and you're running natural selection at extraordinary speed.

00:19:05: The ones that survive have by definition some resistance.

00:19:08: they reproduce.

00:19:09: their offspring inherit the resistance.

00:19:12: within relatively few generations You have a population That the antibiotic cannot touch.

00:19:17: this is not a complicated biological process.

00:19:19: It is natural selection operating exactly as Darwin described it just very fast and with very high stakes.

00:19:26: The result is what the World Health Organization now describes as one of the greatest threats to global health, antimicrobial resistance.

00:19:34: Bacteria that resists multiple antibiotics simultaneously.

00:19:37: MRSA methicillin-resistant Staphylococcus aureus which resists most of the antibiotics routinely used to treat Staphalococcus infections.

00:19:45: NDM producing bacteria some of which resist almost everything we have.

00:19:50: The pipeline of new antibiotics being developed by pharmaceutical companies has essentially dried up because the economics of antibiotic development are unfavorable compared to other drug categories.

00:20:01: We're discovering almost no new antibiotics, though once we have our becoming less effective and a gap between those two facts is where their future problem lives.

00:20:09: Here's why this story comes back into the kitchen To the garden.

00:20:13: There's a thousand year old recipe in an Anglo-Saxon medical text.

00:20:16: Because the crisis of antibiotic resistance has done something unexpected.

00:20:21: It has sent modern science back to look carefully at things people knew before antibiotics existed, not because those things are as powerful a synthetic antibiotics.

00:20:31: they aren't for deep systemic infections but becuase there may contain mechanisms that modern drugs haven't explored.

00:20:38: Because the bacteria havent built resistance to allicin or hydrogen peroxide.

00:20:45: Because the combination of compounds in a natural preparation may work differently from a single purified molecule.

00:20:52: Bald's isalph that anglo-saxon recipe for garlic, leek wine and ox bile was tested against MRSA not by nostalgic medievalists but by microbiologists at The University Of Nottingham who were genuinely looking for new approaches to resistant bacteria.

00:21:07: It worked!

00:21:07: The question why?

00:21:08: And whether mechanism can be developed further.

00:21:11: There is also an entirely different approach being investigated, bacteriophage therapy.

00:21:16: Bacteriophages are viruses that infect and kill bacteria.

00:21:19: They're the natural enemies of bacteria evolved over millions years to hunt specific bacterial strains.

00:21:25: Phage therapy using carefully selected bacterirophages to target specific infections was explored before antibiotics became available largely abandoned when antibiotics arrived And it's now being urgently revisited.

00:21:37: The appeal is specific.

00:21:38: Bacteriophages are extremely precise, where a broad spectrum antibiotic kills bacteria indiscriminately including the beneficial bacteria of your gut microbiome.

00:21:48: A bacteriophage targets only the specific strain it evolved to attack and importantly, bacterirophages also evolve.

00:21:55: they can develop new variants in response to resistant bacteria In a biological arms race that we can potentially guide and direct.

00:22:03: Research.

00:22:03: partnerships between Western science & indigenous knowledge holders are also yielding results.

00:22:09: Canadian researchers working with Indigenous elders have verified that prairie plants, including choked cherry and gumweed specifically target the biofilms —the protective molecular shields—that resistant bacteria use to hide from

00:22:22: antibiotics.".

00:22:23: These are plants that've been used medicinally for generations... ...for reasons they users understood empirically without understanding more accurately.

00:22:31: The pattern is consistent across all of this.

00:22:33: People knew things worked before.

00:22:35: They knew why.

00:22:36: Science is now telling us why, and in several cases the things that worked are providing new starting points for solutions to problems that Europe's synthetic antibiotics helped create.

00:22:45: The kitchen & laboratory are working on this same problem – always were!

00:22:49: So next time you crush a clove of garlic can catch that sharp distinctive smell.

00:22:54: That's Alisson A chemical defence system that evolved millions years ago Triggered by the rupture of a cell wall doing exactly what it evolved to do.

00:23:02: And someone several thousand years ago Notice that wounds treated with it did better and told the next person.

00:23:09: And THAT person, told the NEXT PERSON!

00:23:11: The next time you reach for the honey jar if its good raw honey You're reaching for something that contains a slow release antiseptic system engineered by bees over billions of years at evolution Verified by modern biochemistry and used in hospitals right now... ...and then next time take an antibiotic.

00:23:29: If you take it correctly finish whole course.

00:23:31: only when it's actually a bacterial infection, you are borrowing a weapon from a mole.

00:23:36: A weapon that a woman called Mary Hunt or possibly an anonymous housewife with good eye for interesting fruit helped make available to the world From a cantaloupe in Illinois.

00:23:47: The survival cabinet is not historical thing.

00:23:49: It is living things In your kitchen, medicine cabinets and laboratories trying figure out what comes next.

00:23:56: History isn't just museums.

00:23:58: Sometimes its in the jar of honey at back And it has been working for four thousand years.

00:24:04: If this episode made you look at your kitchen differently, the garlic and honey in small ordinary things that turn out to have extra-ordinary histories – That's exactly what I'm here for!

00:24:13: The Hidden Life of Things is on Spotify, Apple Podcasts & wherever you listen A follow or a like is encouraged.

00:24:20: as if someone interested in medicine, history and long human fight against infection send these to them.

00:24:27: Here's your clue.

00:24:28: next time It is probably holding something together right now somewhere within five meters of where you're sitting.

00:24:36: You have used it without thinking, children use at school, artists in studios and engineers in factories.

00:24:42: Surgeons have used versions inside human bodies – over two hundred thousand years old!

00:24:47: The oldest known example was made by Neanderthals not Homo sapiens.

00:24:52: Neanderthals from Birch Bark Tur suggesting that the ability to make it predates our own species.

00:24:58: It has been made of horse hooves, fish bones and tree sap and insects from milk or natural rubber from synthetic polymers invented in the twentieth century.

00:25:07: It's used for repair broken pottery, assemble musical instruments build aircrafts stick stumps letters hold dentures place attach souls shoes seal wounds surgery any one.

00:25:20: Stranger chapters of its history are the weapon.

00:25:23: What is it?

00:25:24: Stay curious, I'm Alexandra and i'll talk to you next week!