Bugged Page 15
She holds up a chart measuring relative fluorescence units—an analysis of the processed gut content that better resembles stock market trends. “The peaks you see here are where you get amplification at these different regions.” Those peaks signify the DNA profile of the dead. “And so we were able to take out the maggot insides and actually get the profile from the human it was eating off of, which is pretty cool.”
Sanford has been taking maggot samples from people who died of natural causes in an effort to build consistency for this new approach in forensic science. So far, the best samples have been from corpses found indoors with plump flesh fly maggots. I’m certain by the time of this book’s publication, Sanford and Felton will have validated the process, making it a handy tool in homicide investigations.
And for the record, like our friend Lauren at FARF, Michelle Sanford dislikes cockroaches. As she put it: “That’s where I draw the line.”
Though the idea of an insect VIP party in your body might make you squeamish, I hope their nutrient cycling can impart some solace. Still, you don’t have to be a corpse to get friendly with maggots. They have been used in medicine for centuries. Recall the barbed stingers Sanford plucked out of our unlucky Texan. Stings from the order Hymenoptera (e.g., wasps, hornets, etc.) account for the majority of insect-related deaths in America. Ironically enough, that very venom may improve on today’s drugs and save us in ways never before imagined.
Seven
You Just Squashed the Cure for Cancer
If you’ve ever been stung, you probably know it’s not as fun and cutesy as the preschool song “Baby Bumblebee,” in which children pretend to clap the assailant. Had they really clapped a bumblebee, they would enter a world of pain via the bee’s muscled, stinging apparatus. Nerves in the stinger would continually inject venom into their hands, which spells out big-time ouchy. Daredevil entomologist Justin O. Schmidt indexed the intensity of bee, wasp, and ant stings (observed naturally or induced on himself) from 21 species in 1984, ranking the pain from 0 to 4, from “no pain” to “traumatically painful.” Schmidt clearly described the sensation caused by the “mechanics” but was fuzzy on the “chemical nature” of the pain and damage—a mystery, he mentions in his recent memoir, The Sting of the Wild, that chemists still have not solved. How much pain can humans endure? For a reference point, honeybees ranked at a 2. Bullet ant venom, however, caused a sensation like “walking over flaming charcoal with a 3-inch nail embedded in your heel.” To date, Schmidt has been bitten by 150 species (which has luckily saved others from revisiting the experiment). But when it comes to venom qualities and other buggy secretions, there are daring individuals who seek promise rather than peril. Getting stung is something worth singing about.
Entomotherapies, the medicinal uses of insects, have existed for millennia. Some Westerners, though, remain skeptical of the process—with good reason. The long history of entomotherapies seesaws between early medicine and straight up superstition.1 In India, carpenter ant jaws have been used to suture gashes since 3000 BCE. The Ebers Papyrus—an Egyptian medical guide from 1500 BCE—lists a recipe for psychological afflictions: “Take a big scarab, cut off its head and wings, boil it, put it in oil and apply as an ointment to the affected person’s body. Then cook the head and wings in snake’s fat and give it to the patient to drink.” Dioscorides, a Greek physician circa the first century CE, wrote that crushed bedbugs crammed up the urethra combated bedwetting. Twelfth-century Germans, according to a Benedictine abbess, injected ants still very much alive into people suffering from fatigue. Elizabethans mixed rabbit urine with powdered earwigs for a concoction poured into the ear canals of deaf people. Red ants’ acidic secretions2 assist wounded Thai as an antiseptic. And a case of chicken pox in China? Try a cattle tick prophylactic. Actually, to date, China has concocted over 1,700 different drugs from arthropods. And nearly one-third of Hong Kong residents drink royal jelly bee extract, which clinical trials found good for depression.
But the true medical secrets of these insects—excruciating Hymenoptera venoms included—are only now being tapped. Drug discovery in nature from the 1960s up through the ’90s shifted focus toward plants. “Insects,” Georgia entomologist Aaron Dossey tells me, “fell into the cracks.” His research, entitled “Insects and Their Chemical Weaponry,” proceeds to lay out hypothetical game-changers. A similar paper, entitled “Bugs as Drugs,” written a couple of years earlier by Miami doctor E. Paul Cherniack, notes: “Although medical practitioners in more economically robust countries may prefer conventional treatments, it may be more a result of squeamishness rather than science.”
South Americans had known this for some time. When arthritis became too much to bear, they’d stick their inflamed joints into the “tree of the devil” where ferocious Hymenoptera fire ants (Pseudomyrmex triplarinus) nest. Natives voluntarily received venomous bites to send their rheumatoid arthritis into remission. Roy Altman of the University of Miami milked that extract for a double-blind study in 1984. Sixty percent of the venom-treated patients experienced a significant reduction in their swollen joint index. Four years ago, researchers from Brazil’s University of São Paulo State analyzed fire ant venom and identified 46 proteins—a promising potential for new drugs. We now run mass spectrometry over bugs to analyze their chemical makeup. In fact, there’s currently a US patent on Hymenoptera venom for pharmaceutical production as treatment or prevention of nerve-damaging and autoimmune diseases, which include arthritis and multiple sclerosis.
Honeybees have a proven track record in medicine.3 Korean acupuncturists using bee venom–coated needles relieved more pain than traditional therapies thanks to proteins that reduce the ouch factor. Ancient Egyptians treated wounds with anti-inflammatory insect derivatives like propolis—a honeycomb glue made from plant resin. Folk healers fought canker sores with propolis as well, which has been proven effective recently in randomized tests. Today, in vitro studies show an inventory of implicit boons in propolis’s polyphenol, acidic chemicals. Tuberculosis antibiotic? Check. Leukemia suppression? Double check. Leukemia has also been treated with an age-old Asian medicine: blister beetles—natural producers of cantharidin.4 This chemical was found to suppress growing bladder, colon, and oral cancer cell lines, E. Paul Cherniack reports.
Impressive as in vitro studies may be, modern, marketable progress has been made in the field. Some American hospitals use inventions related to folk healing practices. The company Medihoney creates bandage dressings utilizing the osmotic properties found in honey that, like propolis, are anti-inflammatory and moisturizing for burn wounds. Such gauze has been found to reduce heal time by half versus the standard treatment of silver sulfadiazine. Additionally, there is the company called, appetizingly, Medical Maggots. Their containers of sterile maggots (Phaenicia sericata) are placed—this time on the living—in patients’ post-op wounds and plugged with gauze and tape. Larval therapy debrides necrotic tissues and has also improved nonhealing venous ulcers, as well as abscesses and gangrene. A study done on 86 patients showed a “66- to 100-percent reduction of wound size.” (Big thanks goes to the antibacterial secretions from the maggots’ guts.) Those claims explain the 5,000 lab-grown, myiasitic maggots delivered to US hospitals every week in the 1990s. About 20 are needed to treat a square-inch wound. A 2007 study promoting their use estimated 50,000 bottles worth of “medical-grade maggots” were delivered to hospital patients in 20 countries.
Mayans made use of the medical benefits of maggots, as did soldiers in Napoleon’s army wounded on the battlefield. Those attended by maggots had a better chance of leaving with their limbs intact. This isn’t bad, considering the numerous beatings that bugs delivered to Napoleon in his pursuits of conquest. “Although these insects were troublesome,” wrote one of Napoleon’s army surgeons, “they expedited the healing of wounds by shortening the work of nature, and causing the sloughs to fall off.” And beginning with the US Civil War and later World War I, myiasis was used to treat open infections thanks
to the work of William Baer. The French emperor was also aided by another bug, though not in war. Leeches5 literally saved his butt.
Napoleon had a classic case of hemorrhoids. (Conquering nations is stressful, okay?) But a shtickle of Preparation H wasn’t yet available. Leeches, which leave a mark said to resemble the “Mercedes-Benz emblem,” writes hematologist Amiram Eldor, have saliva with antihemostatic agents that “delay clot formation.” You get where this is going. It’s harder to imagine the predicament Napoleon’s physician faced. Now if you would, dear dictator, kindly remove your breeches and spread your cheeks … You may feel a slight nip. This sort of therapy has proven a success for arterial repair and is growing in use in areas such as plastic surgery where improved blood flow helps engorged organs.
Venom, which in medicine functions as a yin and yang, is also making its way into operating rooms. Take deathstalker scorpions. Responsible for hundreds of deaths a year, the world’s most poisonous arachnid may also be used as a new standard in brain tumor surgery.
At the PopTech convention in 2013, Seattle brain cancer researcher Jim Olson projected an image of a cancerous canine brain tumor illuminated in fluorescent wonder midsurgery, shocking the crowd. Deriving the peptide chlorotoxin from Israeli deathstalker scorpions, Olson reengineered the cancer-binding protein to act as a distinguishable “flashlight” for neurosurgeons, who normally accidentally extract healthy brain tissue while trying to ensure they’ve removed all traces of cancer. Precautionary gray matter removal impairs patients’ neurologic function—an unfortunate necessity in this game of millimeters. But Olson’s “Tumor Paint”—scorpion peptides capable of penetrating the impenetrable blood-brain barrier—guides surgeons “100,000 times more” accurately than MRI scans. The peptides also target the lymph channels in which cancer cells travel undetected during surgery. Gliomas and astrocytic tumors become surgical “road maps” in organs, ablaze in vibrant green hues.
Human clinical trials began in December 2013 in Australia. US trials began in late 2014, one site being Los Angeles’s Cedars-Sinai Medical Center. Various studies have also found that the scorpion’s chlorotoxin was a potential visual guide for other body parts, including breast, liver, kidney, prostate, and lung tissues. But Tumor Paint, because it was a bug derivative, seemed far-fetched. Initial grants submitted to national health institutions were turned down for being “highly speculative,” Olson told the PopTech crowd. But families who had faith in the pediatric oncologist donated $5 million to the research. More compounds are emerging. Flublok, a flu vaccine with a three-week production rate (as opposed to the typical six months) that was recently approved by the FDA, uses viral DNA from fall armyworm moth ovaries.
Olson’s separate venture, Project Violet, aims to design drugs from chemicals found in plants and animals, repurposing proteins as Olson has done with Tumor Paint. Currently his researchers, in addition to University of Queensland scientists, are examining the cancer-killing proteins in funnel web spiders, one of the world’s deadliest arachnids. Insects may also end our antibacterial plight. Using the same deathstalker scorpion derivative, virologists in China modified the peptide to kill E. coli and MRSA bacteria—the latter causes the ever-contagious staph infections in hospitals. “Drugs are encoded in their DNA,” Olson said. “And they’ve had millions of years to evolve.”
Biochemists have other crawlies under their microscopes. “Earthworms,” E. Paul Cherniack writes in Alternative Medicine Review, “have a rudimentary immune system and contain antimicrobial and antineoplastic substances.” One, called eisenin, “destroyed” cancerous tumor cells in humans. Prialt, derived from a snail venom peptide known as ziconotide, has become a painkiller substitute for morphine, especially when morphine tolerance becomes an issue. The drawback, however, is that unlike chlorotoxin, ziconotide can’t pass through the blood-brain barrier; it therefore has to be injected directly into the spinal column. A study from the Washington University School of Medicine in St. Louis shows that melittin in bee venom may offer hope for couples with one HIV-positive partner who’d like to have children. Melittin was shown in vitro to break through “the protective envelope that surrounds [the] virus” and destroy its basic structure, leaving cells in sperm and vaginal tissue lining unharmed.
Meanwhile, the number of superbugs, i.e., multi-drug-resistant bacteria, has swelled over the past decades due to our habitual overuse of antibiotics. Twenty-three thousand people die annually in the United States from infections for which multiple antibiotics exist. However, a group of researchers from the University of Nottingham found substances in the brains of locusts and cockroaches that kill superbugs. Because cockroaches are coprophages, i.e., poop eaters, they evolved hardy antibacterial agents.
This shifting, twenty-first-century view of insects is not only affecting medical science, but robotics as well. If we look back at the history of technology, the list of bio-inspired devices goes on and on.
“Technical innovation,” writes Professor Gerhard Scholtz of the Humboldt University of Berlin, “is sometimes the product of the observation of nature.” He attributes the invention of the wheel to dung beetles: “This rolling activity is one of the most amazing actions in the animal world and forms a combination of various techniques and a distinct art of craftsmanship and engineering … The combination of rotation around an axis, making use of the low friction resistance of circular and smooth surfaces to transport a heavy load, shows the closest degree of similarity to a wheel that I can think of.”
Insects are proven catalysts for spurring innovation. As that lovely old-timer Aristotle once mused: “If one way be better than another, that you may be sure is Nature’s way.”
* * *
Recall the Spanish song “La Cucaracha,” about an unlucky cockroach? To help me cross the scientific intersection of insect and technology, I’ve enlisted a tan and blotchy Blaberus discoidalis to undergo transformation into an RC car. Now, this might sound like a painful, RoboCop moment, but unlike the five-legged roach limping around in the Mexican ditty, the B. discoidalis will return to normal once again (minus the addition of some headgear). The cyborg conversion kit I’ve purchased, called RoboRoach, comes from Ann Arbor, Michigan, startup Backyard Brains.
The rewired neural impulses work like this: an electrode, a red circuit board, and a battery are glued onto a 10-centimeter cockroach. Silver ground wires inserted into the roach’s antennae stimulate its sensory neurons. When it receives a “spike” through your smartphone’s remote control interface (via the company’s app), the roach gets the impression it has come into contact with an object and turns left or right. These are actions (or pulse widths) you can fine-tune. In a research paper entitled “Line Following Terrestrial Insect Biobots,” scientists Tahmid Latif and Alper Bozkurt aptly describe this type of locomotive control system as “similar to steering a horse with bridle and reins.” Ultimately, the goal of Backyard Brains’ RoboRoach is to educate kids. The electrical brain stimulators guiding the roach are similar to the ones engineers use in cochlear implants and to stimulate neurons for people with Parkinson’s disease.
I call in my special order for B. discoidalis to a reptile pet shop and go pick it up. Given my love for the legend, I name him Bill “Fucking” Murray. (He even shares the actor’s sense of irony and steely eyes.) Out on my apartment balcony, I saw the condensed brick of dirt substrate in half, dump it in a salad bowl, and add water. Voilà! Instant habitat. Plop a leaf of romaine lettuce into a terrarium, and Billy boy is living happy.
Now to address the screaming little PETA protestor inside you. Consider Billy’s brief biography, with 15 or so siblings produced a couple times a year and a likely encounter with the bottom of a shoe if seen in public. Put together, steering Bill “Fucking” Murray with my iPhone via the gigantic, Bluetooth-enabled circuitboard he lugs around—clumsily staggering like a drunken backpacker—gives him worth. And it’s educational. P. B. Cornwell says in his 1968 book The Cockroach: “It is a reasonable assumption that
more cockroaches have been dissected on the laboratory bench than any other insect.” We’ll soon see why. Also, rest assured that after his procedure and test run, Billy will live out the rest of his cockroach life (approximately 20 months) with me.6
Beethoven’s Symphony No. 3 plays through my computer speakers. Inappropriately, it’s on the second movement—a funeral march. I’ve dunked Bill “Fucking” Murray in ice water, inducing hibernation. Surgery tools—toothpicks, Silly Putty, and tweezers—are laid across the table. After his legs stop kicking, I remove him from my beer mug and use a Q-tip to swab water from his head’s shield, called a pronotum. With sandpaper I remove a waxy layer from his exoskeleton, upon which I then Super-Glue the electrode header. Resubmerging him in water, I wait before inserting the “ground” wire into a hole poked in his thorax and clipping his long antennae down to a quarter inch. Seeing as I’m wearing blue surgeon’s gloves and listening to classical music, I can’t help but hear Peter Seller’s Dr. Strangelove narrate the procedure. I vill now take ze antennae and clip zem halfway in order to insert ze electrode wires.
My hands are shaking. The wire is only 0.003 inches in diameter, so it feels like inserting a hair into another hair. The difficulty in accomplishing this and successfully Super-Gluing it in place makes what happens next emotionally trying. In my haste to prep for the operation, I’ve forgotten hot glue gun sticks, which are meant to keep the tangle of wires in place. Billy, in an innate reaction to obscurity, tears out the wires from his antennae while I sleep. Soldering is the only way to repair it, and I’m not entirely ready to do that to him.