Honey Bees on the Mind

ROSEMARY BUSH BLOOMING, buzzing with bees and birds, a reminder of controversies swirling around pollinators and beneficial insect species. The past Entomological Society of America (ESA) annual meeting featured outstanding virtual presentations on honey bees, bumble bees and pesticides with diverse lethal and sub-lethal effects on fertility, learning, memory, etc. A mindless rush to ban neonicotinoids (neonics, a class of pesticides developed originally in Japan to minimize deleterious effects on beneficial insects like honey bees) has resulted in increased use of worse pesticides (some capable of completely wiping out bee populations). Partly to blame are acutely dysfunctional Tier 1-3 regulatory processes hidden deep in the bureaucratic bowels of the EPA.

University of Texas, Austin researchers are among those leading the charge to have the EPA evaluate sub-lethal effects of all pesticides being considered as neo-nic replacements. Not just on honey bees, but also on bumble bees and other non-Apis native bees (includes lesser-known, less-social squash bees, that are important crop pollinators). Using field-realistic micro-colony experiments with bumble bees, Leeah Richardson found chronic, dose-dependent effects from flupyradifurone, a popular neo-nic replacement: At high concentrations, despite normal birth numbers, all bee larvae were dead by the third instar. In other words, normal numbers of bumble bee larvae were being born, but survival to adulthood was zero. But because adult bees survive flupyradifurone sprays, the pesticide is approved for use on open flowers. Thus, EPA policy (whether inadvertent, incompetent or otherwise dysfunctional seems to favor pollinator abortions before adulthood). Pollinator population control surely is not the goal? Perhaps to regulate otherwise would allow accusations of being pro-life, even if it means stopping abortion of pre-adult honey bees?

Regulatory bureaucracies typically have 3 tiers for evaluating agro-chemicals. Tier 1 is lab experiments with the active ingredient to determine the LD50 (lethal dose to kill 50% of the population). Tier 2 is semi-field experiments (e.g. field cages with treated and untreated flowers for comparisons and evaluation of sub-lethal effects). Tier 3 field trials are very rare, only conducted when Tier 1 and Tier 2 data are inconclusive. “Sub-lethal assessments on native bees, bumble bees, solitary bees really need to be carried out in the regulatory process in Tier 1 as a mandatory requirement,” said UT Austin’s Harry Siviter, who found no advantage from neo-nic replacements such as sulfoxaflor. “Otherwise we are just replacing one insecticide with others that have similar effects.” In other words, choosing winners and losers in the agro-chemical marketplace in an almost arbitrary, nonsensical manner. Welcome to Alice in EPA Land.

Lars Chitka’s new book, The Mind of a Bee (Princeton Univ Press, 2022), is stranger in some ways than Lewis Carroll’s Alice’s Adventures in Wonderland. “Understanding the minds of alien life-forms is not easy, but if you relish the challenge, you don’t have to travel to outer space to find it,” writes Chitka. “Alien minds are right here, all around you. You won’t necessarily find them in large-brained mammals—whose psychology is sometimes studied for the sole purpose of finding human-ness in slightly modified form. With insects such as bees, there is no such temptation: neither the societies of bees nor their individual psychology are remotely like those of humans. Indeed, their perceptual world is so distinct from ours, governed by completely different sense organs, and their lives are ruled by such different priorities, that they might be accurately regarded as aliens from inner space. Insect societies may look to us like smoothly oiled machines in which the individual plays the part of a mindless cog, but a superficial alien observer might come to the same conclusion about a human society. “

“Each individual bee has a mind,” writes Chitka. “That it has an awareness of the world around it and of its own knowledge, including autobiographical memories; an appreciation of the outcomes of its own actions; and the capacity for basic emotions and intelligence—key ingredients of a mind. And these minds are supported by beautifully elaborate brains. As we will see, insect brains are anything but simple. Compared to a human brain with its 86 billion nerve cells, a bee’s brain may have only about a million. But each one of these cells has a finely branched structure that in complexity may resemble a full-grown oak tree. Each nerve cell can make connections with 10,000 other ones—hence there may be more than a billion such connection points in a bee brain—and each of these connections is at least potentially plastic, alterable by individual experience. These elegantly miniaturized brains are much more than input-output devices; they are biological prediction machines, exploring possibilities. And they are spontaneously active in the absence of any stimulation, even during the night.”

“To explore what might be inside the mind of a bee, it is helpful to take a first-person bee perspective, and consider which aspects of the world would matter to you, and how,” writes Chitka. “I invite you to picture what it’s like to be a bee. To start, imagine you have an exoskeleton—like a knight’s armor. However, there isn’t any skin underneath: your muscles are directly attached to the armor. You’re all hard shell, soft core. You also have an inbuilt chemical weapon, designed as an injection needle that can kill any animal your size and be extremely painful to animals a thousand times your size—but using it may be the last thing you do, since it can kill you, too. Now imagine what the world looks like from inside the cockpit of a bee. You have 300 degree vision, and your eyes process information faster than any human’s. All your nutrition comes from flowers, each of which provides only a tiny meal, so you often have to travel many miles to and between flowers—and you’re up against thousands of competitors to harvest the goodies. The range of colors you can see is broader than a human’s and includes ultraviolet light, as well as sensitivity for the direction in which light waves oscillate. You have sensory superpowers, such as a magnetic compass. You have protrusions on your head, as long as an arm, which can taste, smell, hear, and sense electric fields. And you can fly.”

Honey bee research has been a source of inspiration and innovation, and many cite Karl von Frisch, celebrated for his research on bee dances as a form of communication. Von Frisch shared The Nobel Prize in Physiology or Medicine 1973 with Konrad Lorenz and Nikolaas Tinbergen “for their discoveries concerning organization and elicitation of individual and social behaviour patterns”. Thomas D. Seeley of Cornell University writes in the 2022 Annual Review of Entomology: “In the 1920s, Karl von Frisch described a forager producing this dance as follows: “[she makes] trembling movements forward and backward, and right and left”. The meaning of this strange behavior remained a mystery to von Frisch for more than 50 years, and near the end of his career he wrote, “I think it tells the other bees nothing. . .and perhaps is comparable to the condition that Florey has described as a neurosis”.

“I solved this mystery in the early 1990s when I discovered that a nectar forager produces a tremble dance when she visits a rich nectar source but then, upon returning home, has difficulty finding a bee willing to receive her nectar load,” writes Seeley. “The tremble dance calls bees to work as nectar receivers at the start of a nectar flow, just like the whistle atop a sardine factory in Maine calls villagers to work as sardine packers when fishing boats arrive laden with herring. It was thrilling to discover the meaning of this dance. Martin Lindauer once told me that Karl von Frisch had said that he would award a prize to whoever deciphered the message of the tremble dance. Alas, he died in 1982, nine years before I solved this puzzle. My studies of how a honey bee colony nimbly and wisely allocates its foragers among flower patches, despite never-ending changes in the locations of the richest ones, did lead to a different prize some years later. This bee work inspired two computer scientists at Georgia Tech to create the Honey Bee Algorithm (HBA). The HBA is widely used in internet hosting centers (analogous to hives) to optimally allocate webservers (analogous to foragers) among jobs (analogous to flower patches), so it is integral to the multi-billion-dollar industry of cloud computing. In 2016, the American Association for the Advancement of Science awarded me and four professors of engineering at Georgia Tech—John J. Bartholdi, Sunil Nakrani, Craig Tovey, and John Vande Vate—its Golden Goose Award. This award recognizes esoteric research that proves extremely valuable (i.e., that lays lots of “golden eggs”).”

In the German to English translation of his 1953 book, The Dancing Bees, Von Frisch wrote: “SUPPOSE German and English bees were living together in the same hive, and one of the Germans found a lot of nectar: its English companions would easily understand what it had to say about the distance and direction of the find…If we use excessively elaborate apparatus to examine simple natural phenomena Nature herself may escape us. This is what happened some forty-five years ago when a distinguished scientist, studying the colour sense of animals in his laboratory, arrived at the definite and apparently well-established conclusion that bees were colour-blind. It was this occasion which first caused me to embark on a close study of their way of life; for once one got to know, through work in the field, something about the reaction of bees to the brilliant colour of flowers, it was easier to believe that a scientist had come to a false conclusion than that nature had made an absurd mistake. Since that time I have been constantly drawn back to the world of the bees and ever captivated anew. I have to thank them for hours of the purest joy of discovery, parsimoniously granted, I admit, between days and weeks of despair and fruitless effort.”

As has been demonstrated time and time again, nothing is ever conclusively established and beyond challenge in science. Though for periods of time beliefs get set in stone until demolished (1,500 years in the case of some of Aristotle’s nature observations). In the 1920s and 1930s, Nobel Prize-winning immunologists and the American Medical Association doubted the existence of phages (viruses that kill bacteria) and prohibited research on the subject, until finally proven wrong with the invention of the electron microscope. Perhaps it will be the same with the much-contested CO2 climate change hypothesis, currently enthroned on a golden pedestal and considered beyond discussion. Change is a constant, as Adrian Horridge documents in his history of insect vision.

In his book, The Discovery of a Visual System: The Honeybee (CABI, 2019), Adrian Horridge, a honeybee researcher in the UK and Australia since at least 1945, puts forth his controversial history of honeybee visual research. “Beside this saga of contending personalities, this is in fact a serious book that attacks the detail and gist of the compound eye of a typical day-flying insect…The topic of this book is the much-needed revision that puts insect vision as exemplified by the bee, and dim-light vision in other insects, back on track. The new paradigm for visual inputs of the compound eye is one tonic colour blue and two derivatives that are rates of change in blue and green receptor channels. I hope that the novel prospect will be of interest to engineers of robot vision…There is universal inertia against innovation because it is expensive and requires thought, hard work and persistence, and then disrupts set ways. Forces for conformity are now a universal and growing danger that should be resisted. But worst of all, innovation implies an escape from bureaucratic control.” Indeed, insect optics research applied to fiber optics helps enable the World Wide Web and Internet to link computers worldwide at near the speed of light -a major global disruption of social patterns and cultures.

“Already, two major innovations of practical importance have emerged directly from our studies of insect vision,” writes Horridge. “In 1972, from the optics of fly eye, Allan Snyder discovered how the light gets into the light guides. The details were copied into the design of the fibres that carry light pulses for extreme distances in the World Wide Web (Chapter 4). In 1989, Srinivasan, Lehrer, Zhang and I discovered that insects detect a panorama of range by signals created by their own motion, not of objects, and Srinivasan later completed the installation of the resulting applications into mobile vehicles that fly with a computer on board (Chapter 9). The future will bring another important development: reverse engineering of insect vision, simply because insects are examples of extremely sophisticated and well-adapted visual mechanisms at exactly the right level of complexity to be copied into silicon for practical applications, quite unlike our own vision. Moreover, many neurons in an insect, perhaps all, are individually identifiable, and the wiring diagram is also constant, so that we can repeatedly return to precisely the same circuit, neuron or synaptic connection, with a variety of different techniques.”

“As yet, we have no firm circuitry or formal connections in the bee beyond cues and their coincidences,” writes Horridge. “The ways that preferences are established, modified and remembered remain a mystery. We have no idea how bees reach decisions. We have not identified the points where the layout of the two-dimensional image on the eye disappears into responses of line-labelled nerve cells, where odour signals are combined with vision, where traces of the image finally disappear in decisions such as ‘avoid’ and ‘attract’, or where meaningful visual cues are stored in memory. We do not even know whether memory is located at every synapse where the signal passes, or in special localized centres, or in both. A similar state of ignorance applies to every other animal brain, but the bee is one animal where progress is possible, perhaps with the aid of large tropical species.”

Natural Nicotine Heals Honey Bees

NEONICOTINOID INSECTICIDES (e.g. thiamethoxam, imidacloprid, clothianidin) developed at Bayer Japan as safer alternatives (e.g. to human spray applicators) to the natural nicotine once widely used by farmers and gardeners, is now suspected of contributing to honey bee health problems like learning disorders and colony collapse. In contrast, natural nicotine, found in honey produced by bees working tobacco fields, as well as in pollen, nectar, leaves and other plant parts, is a nutrient and medicine helping to heal weak honey bee colonies, said Susan Nicolson of South Africa’s University of Pretoria at “Entomology Without Borders,” a joint meeting of the International Congress of Entomology (ICE) and the Entomological Society of America (ESA) in Orlando, FL.

Natural nicotine, even if produced organically in a sustainable recycling sort of way from tobacco waste products, is mostly shunned in organic farming and gardening. “Over 120 million sites will be returned on a web search on tobacco, but most will not be associated with plant science,” wrote USDA-ARS researcher T.C. Tso in Tobacco Research and Its Relevance to Science, Medicine and Industry. “Many plant scientists in academic institutions cannot obtain grant support for projects using tobacco as a research tool. Some even have to avoid tobacco because of the applying of ‘political correctness’ to academic research. The tobacco plant has served as a valuable tool since the dawn of plant and biological sciences, so it is indeed a great loss to scientific progress that a research tool already invested with so many resources and about which there is such abundant knowledge and such great potential for new advancement is now being wasted.”

Honey bees readily consume bitter alkaloids such as nicotine mixed in sugary plant nectars. Adult honey bees excel at detoxifying alkaloids such as nicotine, which should not be surprising, as survival depends on it. Younger, larval honey bees have fewer enzymes to detoxify nicotine, but also survive quite well even when their royal jelly contains high levels of nicotine. Honey bees and insects immune to nicotine, such as green peach (peach-potato) aphids, transform nicotine into less toxic butanoic acid. A knotty question naturally arises: If natural nicotine heals honey bees, why are synthetic neonicotinoids so terribly different? Are natural compounds like nicotine inherently more beneficial and their synthetic analogs (e.g. neonicotinoids) inherently bad, perhaps due to subtle differences in molecular structure? If bees and other pollinators are a major concern, perhaps natural product restrictions on nicotine need to be relaxed to provide competition to the synthetic neonicotinoids.

“Alkaloids, especially in the nicotine family, have been the main focus of tobacco research because alkaloids are the characteristic product of tobacco,” writes Tso. Dozens of other tobacco molecules are relatively overlooked, including sugar compounds providing least-toxic botanical insect and mite control. Anabasine (neonicotine), an alkaloid found in tobacco and other plants, has also been widely used as a natural insecticide. Strangely enough, anabasine is also an insect attractant and a poison gland product of Aphaenogaster ants. In a strange urban twist to the wild bird practice of lining nests with medicinal herbs emitting essential oils counteracting parasites: Researchers in Mexico discovered urban birds lining nests with cigarette butts to similar advantage. In times past, organic gardeners soaked cigarette butts in water to get a nicotine spray brew. Historically, most commercial nicotine insecticide used on farms and gardens was a sustainable tobacco waste extract.

There are 60-80 described tobacco or Nicotiana species, some available in seed catalogs and grown as ornamentals. Most Nicotiana species grow wild in the Americas, with some in Australia and Africa. “Tobacco plants are easy to grow and have a short growing period,” writes Tso. “Each tobacco plant may produce 14 g or about 150,000 seeds which may provide seedlings for 2 to 5 acres (1–3 ha) of field tobacco, depending on the type.” In Europe, oil extracted from tobacco seeds is being explored for an alternative bio-diesel fuel industry, with dry leftovers as animal feed.

Native American Nicotiana species are being integrated into China’s ancient agricultural interplanting tradition. When tobacco is interplanted in vineyard rows, tobacco roots and grape roots intermingle. Perhaps some sort of biological soil fumigation occurs. Whatever the mechanism, vineyards are cleansed of soil-dwelling phylloxera aphids, a pest that almost destroyed wine grape growing in France in the 1800s and is still a worldwide problem. According to the journal Chinese Tobacco Science, intercropping tobacco with sweet potato also alleviates soil and other pest problems, maximizing profits per unit area of land. Burley tobacco is intercropped with cabbage and other vegetable crops, according to the Journal of Yangtze University (Natural Science Edition).

Neonicotinoids are soluble in water and absorbed systemically by plants, and some are sprayed on urban lawns and landscapes. However, over 80% of synthetic neonicotinoids are applied to seeds prior to planting hundreds of millions of acres of corn, soybean, sunflowers and other crops. In Canada’s Ontario and Quebec provinces, 100% of corn seed is treated with neonicotinoids, said Nadejda Tsvetkov of Toronto’s York University at “Entomology Without Borders.” Though neonicotinoids were seldom found in corn pollen samples, somehow, perhaps by water transport, neonicotinoids are finding their way into clover and willow tree pollen far from corn fields.

“For a lot of farmers it is hard to get seeds untreated, especially corn,” as commercial seed is routinely treated with neonicotinoids regardless of need, said the University of Maryland’s Aditi Dubey at “Entomology Without Borders. In Maryland and other mid-Atlantic USA states where low pest pressures are the norm, neonicotinoid seed treatments are both unneeded and counterproductive. In 3-year Maryland rotations with double-cropped soybeans, winter wheat and corn, sowing seeds treated with thiamethoxam or imidacloprid reduced beneficial predatory ground beetles and increased slug damage to crops. Mid-Atlantic USA farmers typically apply 4 unnecessary prophylactic seed treatments every 3 years. Besides reduced biocontrol and more pest damage, soil accumulation over time is a disturbing agro-ecosystem possibility.

Alternative seed treatments include natural plant hormones such as salicylic acid and methyl jasmonate, which induce a natural immunity called induced systemic acquired resistance (SAR). Crops such as lettuce and argula (rocket) grown from seed treated with salicylic acid and methyl jasmonate also release volatile gases repelling pests such as sweet potato whitefly, a major worldwide pest, said Ben-Gurion University’s Mengqi Zhang at “Entomology Without Borders,” a gathering of 6,682 delegates from 102 countries. Numerous botanical materials and microbes have also been investigated around the world as alternative seed treatments.

A proactive approach to honey bee and bumble bee health includes a diversified landscape sown with herbs and medicinal botanicals for self-medication, not just natural nicotine from tobacco nectar or other sources. Thymol, an essential oil found in thyme and many other plants, is already sprayed in hives by beekeepers to combat Varroa mites. At “Entomology Without Borders,” North Carolina State University’s Rebecca Irwin reported laboratory choice tests where bumble bees rejected nicotine. In field tests, bumble bees were given a choice of different colored flowers each with a different botanical such as thymol, nicotine, anabasine and caffeine. Bumble bees only selected flowers with thymol to self-medicate. Interestingly, thymol and other herbal essential oils also synergize nicotine, boosting effectiveness against disease pathogens and perhaps also minimizing the likelihood of colony collapse.

Landscapes and hedgerows sown with medicinal plants such as thyme, sunflower and foxglove minimize bumble bee disease transmission, said Lynn Adler of the University of Massachusetts, Amherst. The current USA farm bill will actually pay farmers to plant bee-friendly sunflower edges or hedgerows around canola fields. Antimicrobial and medicinal honeys derived from sunflower, bay laurel (Laurus nobilis), black locust, etc., also effectively combat bee diseases like chalkbrood and foulbrood, said Silvio Erler of Martin-Luther-Universität in Halle, Germany at “Entomology Without Borders.”

Bee pharmacology is also useful in human medicine. In Oaxaca, Mexico gangrene is stopped and wounds are healed by combining maggot therapy and honey, reported Alicia Munoz. Maggot therapy uses sterilized (germ-free) green bottle fly maggots to disinfect and cleanse wounds by eating unhealthy tissues and secreting antibiotics, allowing healthy pink tissue to grow back under honey-soaked gauze. This cost-effective approach reduces hospital stays, lowers morbidity and can eliminate the need for surgery. It may sound yucky, but for diabetics and patients with bed sores or wounds where surgery is medically impossible, a few maggots and a little honey is preferable to amputating wounded or infected limbs.

Cancer-fighting bee propolis products were touched upon at “Entomology Without Borders” by Chanpen Chanchao of Chulalongkorn University in Bangkok, Thailand, where hives of stingless bees are reared like conventional honey bees. Cardol, a major component of propolis from the Indonesian stingless bee, Trigona incisa, causes early cancer cell death by disrupting mitochondrial membranes and “producing intracellular reactive oxygen species (ROS).” ROS are essential to energy, immunity, detoxification, chemical signaling, fighting chronic and degenerative diseases, etc. Cardol “had a strong antiproliferative activity against SW620 colorectal adenocarcinoma,” killing colon cancer cells within 2 hours, followed by complete cell necrosis within 24 hours. Thus, cardol is an “alternative antiproliferative agent against colon cancer.”

Sunflower Power & Health

WITH PERHAPS 25 MILLION ha (62 million acres) of sunflowers grown for seed oil worldwide, sunflower diseases and pests and their remedies have a global impact. “Sunflower oil can be used as an alternative or additive to diesel fuel to create biodiesel, a clean-burning alternative fuel produced from a renewable resource,” wrote G.J. Seiler, one of many worldwide contributing authors to the Compendium of Sunflower Diseases and Pests, a book produced by the American Phytopathological Society (APS), a scientific group whose essence includes plant doctoring, discerning what makes for healthy versus diseased plants. “Use of the product may decrease farmers’ dependence on petroleum fuels by substituting ‘farm-grown’ fuel for use in diesel engines. For use in diesel engines, sunflower oil requires more extensive purification, including removal of waxes and gums. Minor engine modifications, such as improved fuel filters, are also necessary to burn any vegetable oil. Since the energy content of sunflower oil is less than that of diesel fuel, consumption is greater and power output is less.” However, the high-protein residues leftover from sunflower oil extraction have the right amino acid balance to mix with soybean meal to grow healthy chickens and livestock, a virtuous ecological cycling of sunflower plants.

Indeed, in Argentina’s southern Pampas, if you get the planting times right, sunflower and soybean are compatible as intercrops. Working in agriculture, I observed sunflower border rows or perimeters around conventional crop fields attracting pollinators and natural enemies providing biological control of pests. However, sunflowers are so attractive to beneficial insects that they do not want to leave. Thus, sunflower stalks need vigorous shaking to get green lacewings and natural enemies of aphids and other pests to take flight into adjacent crops needing protection. At the moment, fields of GMO canola producing high quality cooking oil are displacing sunflower fields in many areas. But the APS sunflower Compendium awakened my love for sunflowers, as even the diseases afflicting the plants have a certain beauty under the microscope. So, I can see the APS sunflower Compendium serving as an outstanding library reference for biology teachers and students looking for projects in sunflower-growing areas.

R.M. Harveson opens the APS sunflower Compendium with a brilliantly concise narrative chronicling the journey of sunflower seeds from their native North America to Russia, where innovative plant breeders painstakingly created the first modern sunflower seeds high in oils, providing the platform for today’s worldwide sunflower industry. The Mennonites, an anti-violence religious group migrating from Germany (Prussia) and a war-plagued Europe to Russia in the 1780s for free farm land promised by Catharine the Great, pioneered commercial sunflower oilseed farming in a harsh landscape long thought unsuitable for even subsistence farming. Their descendants were lured to Saskatchewan and Manitoba, Canada to create North America’s sunflower industry. During World War II, when “securing the fields of Ukraine was a major objective of Adolf Hitler’s war on Russia,” sunflower oil was a superior antifreeze, lubricating World War II weapons that froze with conventional gun oils. Joe Pappalardo’s excellent and entertaining book, Sunflowers: The Secret History: The Unauthorized Biography of the World’s Most Beloved Weed (Overlook Press) adds color and specifics, and is cited in Harveson’s “Selected References” in the APS Compendium.

Personally, I love the feel on my head and hair of a shampoo blending organic sunflower oil, citrus oils and herbs; and organic sunflower seeds at breakfast supply trace minerals like zinc, which is often deficient in produce grown in local California soils. Sunflower sap, which occasionally has been used medicinally, contains terpenoid compounds that show potential as alternative botanical pesticides. As ingredients in traditional medicines, wild sunflowers have been used for everything from wound healing and rattlesnake bites to combating infection and pain relief. Modern medical uses include topical oil formulations with sunflower oil to improve skin health, fight fungal infections, relieve inflammation and itchy, dry skin, and in dentistry to improve the gums.

Seed hulls of certain sunflower varieties are traditional sources of yellow, ruby red, purple, and black dyes or colorants (e.g. anthocyanins) useful in body painting, cosmetics, foods and textiles. Indeed, some plant breeders are working on a sunflower seed that would be high in oil and have a ruby red husk or hull that could be extracted to replace commercial synthetic red food dyes. Other researchers see the hulls as useful absorbents for wastewater reclamation. But by far, sunflower seed oils (e.g. NuSun for cooking) are the main sunflower item of commerce, and even trade on the commodities futures markets. Sunflowers seeds like Mammoth Russian for eating and snacking or adding to birdseed blends are important crops, but minor compared to the large acreages of sunflower oilseeds grown worldwide.

For various reasons, sunflowers have not become commercialized as a biotech GMO (Genetically Modified Organism) crop, which makes life easier for organic growers. Though perhaps better known from Van Gogh canvases, sunflowers were experimental subjects on the USA’s Apollo space missions. And “sunflowers have been successfully used as vehicles for the phyto-remediation of soil contaminated with heavy metals and radioactive materials (e.g. following the Chernobyl disaster),” wrote Harveson. In March 2011 after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident, sunflowers and sunchokes were among the “alternative technology” plantings to concentrate and remove from soils radioactive cesium, which emits gamma rays and has a 30-year half life.

Sunchokes or Jerusalem artichokes, perennial sunflowers grown for edible tubers high in inulins, are sometimes recommended for diabetes and cardiovascular diseases, being associated with lowering blood sugar and cholesterol. Indeed, Jerusalem artichoke chips have been tested as a snack food alternative to potato chips for diabetics, being almost devoid of starch and fats. Several dozen other sunflower species are known, including one that is 92% pure natural rubber. Most likely sunchokes and other sunflower species including backyard ornamentals are subject to pests and diseases similar to those described in the APS Compendium.

To prevent pests and diseases, as a kind of insurance, perhaps 95% of commercial sunflower seeds are coated with neonicotinoid pesticides (e.g. thiamethoxam, clothianidin) at planting time, according to Michael Bredeson of South Dakota State University in Brookings at the 2015 joint meeting in Minneapolis of the Entomological Society of America (ESA), the American Society of Agronomy, the Crop Science Society of America, and the Soil Science Society of America. Bredeson studied 11 commercial sunflower fields, and found that “the seed treatment failed to improve yield or decrease herbivores.” In other words, quite apart from whatever effects on honey bees and beneficial organisms higher in the food chain, the neonicotinoid seed treatments are mostly a waste of resources and money. Though perhaps they do buy peace of mind for commercial sunflower growers, much like any insurance policy.

But the peace of mind bought by unnecessary early-season pesticide seed treatments may bring ecological food chain effects that cost sunflower growers more money and crop loss later in the season. The neonicotinoid pesticides may enter the food chain via plant nectar, plant tissues and predator consumption of tainted prey. Indeed, Pablo Gontijo and colleagues (2015) reported that sunflower seeds treated with thiamethoxam poisoned minute pirate bugs (Orius insidiosus), which are major predators of aphids, caterpillars, spider mites and other pests. Part of the problem is that the beneficial bugs, besides eating pests, also suck moisture directly from plants and thereby become poisoned by systemic pesticides used as sunflower seed treatments.

Likely the poisoned pirate bugs are only the tip of the proverbial iceberg. At the 2015 ESA meeting, Sirilak Lankaew from RYFCRC in Rayong, Thailand reported that cassava cuttings treated preventively with thiamethoxam provided 1-2 months cassava mealybug protection at the cost of food chain effects on beneficial insects via poisoned cassava nectar. Specifically the wasp Anagyrus lopezi, a cassava mealybug natural enemy, feed on the poisoned cassava nectar and “experience acute mortality for up to 21 days after treatment, and have significantly reduced lifespan for at least 42 days after treatment.” With 8 million farming households in Thailand growing cassava and 70% of Thailand’s small-scale farmers using neonicotinoid pesticides, there is a need for alternative technologies “fully compatible with (naturally-occurring and cost-free) biological control.” In sunflower, something like the APS Compendium to identify the potential problems is a good first step towards minimizing unnecessary pesticide treatments and developing alternative technologies.

One approach to developing sunflower soils that are disease-free and avoiding seed treatments is the opposite of crop rotation. Namely growing the crop repeatedly in the same soil so that disease organisms build up and then are destroyed by natural biological agents. It is like the predator and prey cycle, where pests buildup to high levels and even cause some damage before being opportunistically exploited and knocked down by their natural enemies. This approach, known as building a disease suppressive soil, can take a few years; and is perhaps best suited to patient organic growers with the wherewithal to weather those tough early years, and possessed of a confidence, hope or faith that the natural cycles will eventually play out. Likely the Mennonites whose experiences Joe Pappalardo recounts in his book took this route in turning the barren Ukraine, Russian and Canadian lands into productive agricultural fields in the era predating intensive chemical agriculture.

Another interesting alternative technology with ancient roots is interplanting, the idea of mixing different crops in the same fields. In Pakistan, sunflowers are being considered as a healthful alternative for local cooking oil shortages via interplanting sunflowers with the staple mungbean crop. In Florida, sunflower strips have been proven to attract honey bees and a variety of predators and parasitoids supplying natural biological pest control to adjacent organic vegetables. In China, parts of Asia and Africa, and even the Americas, sunflowers are viewed as an alternative technology to reduce herbicide use. Sunflowers provide natural weed control via shading the ground and natural herbicidal compounds (allelochemicals) toxic to some of the world’s worst weeds, such as dodder and barnyard grass. Multiple benefits if you can get rid of a weed patch, produce beneficial insects and pollinators, and harvest some seeds at the same time.

The health benefits of sunflowers will likely be a key driver for this crop in the future, though medicinal sunflower benefits are far from the cutting edge of agriculture and medical research in the genomic era. Broader medical applications may involve anti-inflammatory and cardiovascular benefits, bone health, detoxification, skin protection (e.g. from light & anti-aging) and anti-cancer effects. Applied to the skin, sunflower oil formulations may reduce bacterial and fungal infections, and are touted by some for premature newborns. In Cuba a product called Oleozon, sunflower oil treated with ozone gas, was registered in 1999 to treat fungal skin diseases (tinea pedis); and can stop bacteria and viruses resistant to multiple drugs.

Interestingly, researchers in Iran writing in the Journal of Food Science and Technology like the idea of infusing highly unsaturated oils like sunflower seed oil with raspberry or related Rubus species (e.g. blackberries) as a GRAS (Generally Recognized As Safe) alternative to preservatives like BHA and BHT. Rubus leaves add other medicinal properties to sunflower oil, “including as astringent, hypoglycemic, anti-diarrhea, anti-inflammatory agents for mucous membrane of oral cavity (mouth) and throat.” Many other oils and herbs may have medicinal value when combined with high linoleic acid sunflower oil. Time will tell.

The whole idea of plant medicines may yet return to modern medical practices for a variety of reasons. “Extended life expectancy is accompanied with an increase in age-related pathologies that include cardiovascular and neurological diseases, obesity, and cancer, conditions that are inflicting an immense pressure on health care costs and quality of life,” write researchers Andrea Doseff and Erich Grotewold at The Ohio State University and Arti Parihar in Ujjain, India, in the book, Pigments in Fruits and Vegetables (Springer, 2015). “Thus, there has been an increased interest in recognizing and understanding the mechanisms of action of active nutritional compounds with health benefits, or nutraceuticals, for the prevention and treatment of various diseases.”

The researchers in India and Ohio note that over 8,000 flavonoid chemicals beyond vitamins have been identified, including a range of anthocyanins like those in sunflowers, “which are responsible for providing colors to fruits and vegetables, and have dietary value as color additives with potential health benefits.” Over 10,000 tons per year of anthocyanins from black grapes alone are consumed every year, and this whole general category of plant pigment compounds has “uses in the prevention and treatment of inflammatory diseases including cardiovascular diseases, obesity, and cancers.” Who knows what concentrated research into sunflowers would reveal?

Pigments of the Imagination: Cochineal’s Renaissance

SAP-SUCKING SCALE INSECTS, such as cochineal, kermes and lac, are sometimes sprayed with pesticides as landscape and crop pests, and other times cultivated as beneficial insects. For example, cochineal secals have provided biological weed control in India, Australia and South Africa where imported prickly pear cactus (Opuntia spp.) hedges have escaped and become rangeland weeds. Cochineal scale insects, bred in ancient Mexico to yield 15%-30% color pigment content, have been grown in the Americas for many centuries on prickly pear cactus as a sustainable, biodegradable colorant crop yielding dyes ranging from red, yellow, orange and brown to pink, lavender and purple (depending on mordant, pH, etc.). Intensely red cochineal has a long and famous history in painter’s palettes, tapestry and fabrics, and has been used for centuries to color or stain tissues red or purple for microscope visibility in biology and microbiology labs, medicine and dentistry. Cochineal scale pigments also color selected beverages, foods (on labels as E-120 & carmine) and cosmetics like lipstick, rouge and nail polish. Biochemistry labs like the cochineal red molecule’s ability to bind or bond with proteins, nucleic acids and fats (lipids). Analytic chemists use cochineal “for photometric determination of boron, beryllium, uranium, thorium, and osmium.” At the cutting edge frontier of science, cochineal pigments are being adapted to “molecular information processing” and computing. The red pigment’s “strong photosensitization and photocurrent switching effects” are being designed into next generation optoelectronic (i.e. light, photon) devices like semiconductors, fuel cells, sensors and photovoltaic solar energy systems.

“In Latin-the indispensable language of Renaissance medical professionals—the word pigmentum signified both a pigment and a drug,” writes Amy Butler Greenfield on page 83 of the paperback edition of her meticulously researched book, A Perfect Red, which follows the parallel rise and fall of the Spanish Empire and the secretive cochineal red export trade. “Artists who made their own paints were often advised to procure cochineal from their local “Drugist” or pharmacy, advice that highlights the fact that Europeans also used cochineal as a medicine,” a practice “at least partly borrowed from ancient Mexico,” where cochineal was used to clean teeth and also dissolved in vinegar and applied as a poultice to cure wounds and strengthen bodily organs. Spain profited more from importing cochineal into Europe than from all its plundered and mined New World gold. When ancient alchemy’s metamorphosis into modern chemistry advanced to synthesizing a less expensive, wider range of brighter dye pigments, the Spanish red dye monopoly was obsoleted and the financial collapse of the steadily weakening empire allowed for a global power shift; the USA, fresh from coast to coast expansion and hot for global colonial-style conquests, easily knocked off the remnant hollow shell of the Spanish Armada in the Caribbean and Philippines in 1898.

Let’s start with cochineal and scale insects as pests, and organic control alternatives, as that is how most people encounter and view scale insects. Parasitoid wasps, lady beetles, birds and many other natural enemies provide biological control of scale insects, but not always enough at the right time. Highly refined petroleum oils, vegetable oils and high-pressure water sprays (with or without soap or surfactants) are among the often used remedies. High pressure water sprays, from a nozzle or heavy overhead rainfall, wash off or injure cochineal scales; and this remedy is sometimes used post-harvest by packing houses to clean fruit prior to shipping. Laboratory studies indicate that epazote (Chenopodium ambrosioides), mint (Mentha spp.) and marigold (Tagetes spp.) extracts applied with emulsifiers are potential organic or environmentally friendly synthetic pesticide alternatives.

At the Entomological Society of America (ESA) annual meeting in Minneapolis I talked with Colorado State University extension entomologist Whitney Cranshaw, whose special spiked shoes for killing white grub beetle larvae beneath the soil surface while walking golf course turf and lawns achieved notoriety in Smithsonian magazine many moons ago. This time he was a lonely entomologist, as out of hundreds of passersby no one was stopping at the poster of graduate student Rachael Sitz reporting on a kermes scale vectoring a bacteria causing drippy blight of red oaks in Colorado. Cranshaw was ecstatic having a customer, and figured I was studying the poster display because the kermes scale was also found in California locales such as San Jose, Mammoth Lakes and Monticello Dam on blue oaks and chinquapin bushes. Actually, I was wondering if this particular kermes scale, which went by the scientific name Allokermes rattani, was related to Old World kermes scales used for centuries by pigment artists in Europe and Asia. According to Cranshaw, workers handling the Colorado kermes scale came away with hands dyed a deep brown. So, perhaps this “pest” scale insect is indeed an untapped resource, similar to cochineal, waiting to be discovered by textile artists, painters and photographers looking for natural organic pigments.

My own interest in these insect pigments is a bit abstract, how to incorporate these pigments into the photographic printing process, inspired in part by viewing Robert Rauschenberg’s vegetable pigment prints with photo images from Indonesia. Cochineal was apparently on occasion used in early color photography printing, dating back to the 1800s and heliochromes, which I surmise are solar prints that also use silver as a light-sensitive pigment. Some modern authors talk of a “green synthesis,” fusing conventional silver nanoparticle photography with cochineal red pigments; but I have not found much on the subject. “Color photography,” U.S. Patent No. 923,019 from 25 May 1909 reads: “To all whom it may concern: Be it known that I, EDGAR CLIFTON, a subject of His Majesty the King of the United Kingdom of Great Britain and Ireland, residing at 3 BeaufortVillas, London Road, Enfield, in the county of Middlesex, England, have invented certain new and useful Improvements in Color Photography…known as the two color process; the three color process; and the four plate process…so that the assemblage gives more or less natural color effects…As the red dye: alizarin (with alumed reliefs), cochineal red (or carmin with ammonia), or magdala red…”

SCALING UP PRODUCTION of pigment scales, versus natural harvest, is often surprisingly difficult. For one thing, about 14,000 individual scale insects are needed to obtain 100 grams of raw cochineal pigment. Far from being dumb savages, ancient Mexico’s New World cochineal growers were superb insect breeders. The best cochineal “breeds” contain 18%-30% pigment by dry weight. Spaniards settling in the New World never mastered the delicate art of cultivating cochineal scale on prickly pear cactus, and instead relied on the indigenous los indios de Mexico, some of whom grew rich on the cochineal trade in what was essentially a free market. Many Spanish colonists found it intolerable that the natives were becoming the richest citizens, and this led to all kinds of frictions and conflicts aimed at turning the natives into poorer, more docile (less uppity) and easier to control colonial subjects. The Spanish were remarkably successful at keeping curious outsiders out of the cochineal production areas for centuries, making the cochineal red dye one of the world’s all-time best kept trade secrets. Most Europeans assumed the grana or granules of cochineal were seeds or plant material, like indigo or madder. On those rare occasions when the secret was revealed, the public refused to believe that cochineal red was literally dried insects. This combination of secrecy and worldwide ignorance allowed the Spanish cochineal monopoly to persist for several centuries and be more lucrative than precious metals.

As any entomology grad student can tell you, the same insect that is an abundant pest can often be impossibly hard to grow when you want it for experiments or as a thesis subject. For one thing, the “insect crop” usually has its own set of pests (called natural enemies), which for cochineal scales includes bacteria, lady beetles, syrphid or hover flies, predatory caterpillars, rodents, reptiles and birds. To prevent “crop failure,” cochineal scales need pampering and protection: 1) from natural enemies; 2) shade to protect from direct sunlight; 3) shelter from heavy rains that wash off and injure the scales. Raising cochineal scales as “farm animals” or “livestock” on prickly pear cactus was often a family enterprise in Old Mexico, an art or skill passed down from generation to generation. The prickly pear cactus itself is still also food, animal fodder and medicine in Mexico. But cochineal grana are no longer treated like money or currency, as it was in Aztec Mexico when cochineal was used in payment of tribute or taxes. In that sense, in contrast to a modern dollar, euro, yen, peso, pound, rupee or digital currency, which cannot be directly used as dyes or medicines, the grana possessed an exquisite versatility and flexibility in ancient times.

CARMINIC ACID, a MEDICINAL CHEMICAL pigment compound extracted from cochineal and first synthesized in 1998, belongs to a class of anti-tumor and antibiotic compounds called anthracycline derivatives, which “are believed to develop their cytotoxic effect by penetrating into the tumor cell nucleus and interacting there with DNA,” write chemists at Gazi University in Ankara, Turkey. Combined with other compounds, cochineal is also active against viruses and other microbes. In Tamil Nadu, India cochineal scale insects collected from cacti are crushed, boiled in water and dried to a powder used against whooping cough and as a sedative. Other traditional uses likely abound.

In nature, cochineal functions as an insect repellent. One theory is that cochineal repels ants, protecting young scale insects before their protective waxy outer covering forms. A carnivorous caterpillar eating the scales incorporates the cochineal dye into its own bodily defenses. A study in the Journal of Polymer Science concluded that cochineal and other natural dyes (madder, walnut, chestnut, fustic, logwood) and mordants (aluminum, chrome, copper, iron, and tin) increased the insect resistance of the wool fabric to attack by black carpet beetles.” Indigo was least effective, and cochineal and madder were most effective except when used with tin and chrome as the mordant or binding agent. I only remember one ESA presentation investigating cochineal as a natural insecticide, and that was back in 2004; the idea was that since carminic acid was already approved as safe for food by the FDA, cochineal could be formulated as an organic bait spray to stop fruit flies without losing organic certification. The researcher theorized that cochineal needs sunlight to be activated as an insecticide, and would thus be ideal for organic agriculture. But as far as I know, the idea was never adapted as an agricultural or quarantine practice.

COMBINING COLOR and HEALING is, however, an idea gaining traction. Carminic acid, a brilliant red compound constituting about 10% of cochineal8, “is one of the most light and heat stable of all the colorants and is more stable than many synthetic food colors,” write Khadijah Kashkar and Heba Mansour in the Department of Fashion Design at King Abdul Aziz University, Saudi Arabia. “Besides the color attributes, recently, also has been reported to beneficial to health with potential antibiotic and antitumor properties. At the beginning of the 21st century it is predicted that many colors will be used for both their additional beneficial functions in the body, as well as, coloring effect.” Whether color and healing were also linked in ancient or Aztec times with cochineal is an intriguing question. Perhaps everything old is indeed new again, but who knows what the ancient New World healers or shaman thought when applying bright red or purple cochineal poultices.

PREVENTIVE MEDICINE might be what to call the combination of organic cotton and natural cochineal dyes to block ultraviolet light from skin contact. Ajoy Sarkar of Colorado State University, writing in the journal BMC dermatology: “The ultraviolet radiation (UVR) band consists of three regions: UV-A (320 to 400 nm), UV-B (290 to 320 nm), and UV-C (200 to 290 nm). UV-C is totally absorbed by the atmosphere and does not reach the earth. UV-A causes little visible reaction on the skin but has been shown to decrease the immunological response of skin cells. UV-B is most responsible for the development of skin cancers…Other than drastically reducing exposure to the sun, the most frequently recommended form of UV protection is the use of sunscreens, hats, and proper selection of clothing. Unfortunately, one cannot hold up a textile material to sunlight and determine how susceptible a textile is to UV rays.” Heavy concentrations of synthetic dyes in synthetic fabrics generally provide good UVR protection, but are not as comfortable as cotton fabrics for warm, humid climates. Generally, the darker the color and the thicker the weave or denser the fabric, the better to protect against UVR. Depending upon the weave (e.g. twill vs sateen), Sarkar reported good to excellent UVR protection with natural dyes such as madder, indigo and cochineal.

COCHINEAL’S 21ST CENTURY RENAISSANCE and resurgence includes harnessing cochineal’s ability to capture (harvest) or route light (photons) and electrons in advanced or next generation optoelectronic devices such as semiconductors, light harvesting antennae, sensors, fuel and solar cells, and molecular information and logic gates for computing devices. I was surprised to learn that natural pigments have a long history in advanced electronics: “As early as the birth stage of lasers, coumarin, which is found naturally in high concentration in the tonka bean (Dipteryx odorata), was used in dye lasers” and “coumarin dye is still the basic active medium for many tunable dye laser sources,” writes M. Maaza (2014) of the University of South Africa. “Extracts from Hibiscus sabdariffa, commonly known as Roselle, carminic acid of the cochineal scale and saffron exhibit exceptional nonlinear optical (NLO) properties of a prime importance in optics.”

THE “NEXT GENERATION” SOLAR CELL replacement for today’s silicon-based solar cells will probably be a dye-sensitized solar cell (DSSC) based on titanium dioxide (TiO2), a semiconductor material that is fused with color pigments analogous to those used in conventional color photography (e.g. silver halide emulsions sensitized by dyes). TiO2 and other metal oxides are widely used in medicine, food preservation, cosmetics, sunscreens, paints, inks and a wide range of electronic devices for sensing, imaging, optics, etc. TiO2 is relatively inexpensive, and deemed low toxicity. Interestingly, TiO2 nanoparticles for solar cells can be produced from cultures of bacterial cells, such as the Lactobacillus sp. found in yogurt or curd, which means an even “greener” solar cell fabrication process.

The scientific roots of the modern solar cell go back to French physicist Edmond Becquel’s discovery of the photovoltaic effect in 1839; and prototype solar cells with efficiencies of 1% or less also date back to the 1800s. Though Albert Einstein explained the photovoltaic effect in 1904, the development of lightweight solar energy cells to power spacecraft in the 1950s. But the DSSC or Grätzel cell is a 1990s’ innovation attributed to Mr. O’Regan and Michael Grätzel. “This new device was based on the use of semiconductor films consisting of nanometer-sized TiO2 particles, together with newly developed charge-transfer dyes,” and had “an astonishing efficiency of more than 7%,” write Agnes Mbonyiryivuze et al. (2015) in the journal Physics and Materials Chemistry.

Next generation DSSCs or photovoltaic cells are currently undergoing a major design transition using natural color pigments like those found in cochineal scale insects. DSSCs with efficiencies in the 10% to 15% range can be manufactured with titanium dioxide (TiO2) nanoparticles bonded on a thin film with a light-sensitive dye utilizing a rare and expensive platinum group heavy metal, ruthenium (Ru; named after Russia). Ruthenium’s relatively high cost and environmental and toxicology concerns are a barrier to commercialization that is spurring the search for substitutes; namely cheaper and more environmentally friendly natural pigment. Companies working “to bring DSSC technology ‘from the lab to the fab’” include “Dyesol, G24i, Sony, Sharp, and Toyota, among others,” write Mbonyiryivuze et al. (2015). “Functional cells sensitized with berry juice can be assembled by children within fifteen minutes, the large choice of colors, the option of transparency and mechanical flexibility, and the parallels to natural photosynthesis all contribute to the widespread fascination. In 2013, the drastic improvement in the performance of DSSC has been made by Professor Michael Grätzel and co-workers at the Swiss Federal Institute of Technology (EPFL). They have developed a state solid version of DSSC called perovskite-sensitized solar cells that is fabricated by a sequential deposition leading to the high performance of the DSSC. This deposition raised their efficiency up to a record 15% without sacrificing stability…this will open a new era…even surpass today’s best thin-film photovoltaic devices.”

“PIGMENTS MAKE NATURE COLORFUL and LIKABLE,” writes Chunxian Chen, a researcher at the University of Florida’s Citrus Research and Education Center and the editor of a 277-page book published by Springer in 2015, Pigments in Fruits and Vegetables: Genomics and Dietetics, which places a heavy emphasis on the nutritional and medicinal benefits of colorful natural pigments like those coloring crops of carrots and sweet potatoes orange and radishes and tomatoes red. “Plant pigments usually refer to four major well-known classes: chlorophylls, carotenoids, flavonoids, and betalains…Chlorophylls are the primary green pigments for photosynthesis. The latter three are complementary nongreen pigments with diverse functions…The importance of colors in living organisms cannot be overstated…they are biosynthesized behind the scenes in living organisms and ultimately ingested in daily diet.” Presumably this daily consumption and medicinal benefits makes natural pigments in general logical and sustainable alternatives to expensive heavy metals in “green” electronic, computer and solar energy cell designs.

Agnes Mbonyiryivuze, in her 2014 dissertation titled “Indigenous natural dyes for Gratzel solar cells: sepia melanin,” provides a readable overview of solar energy cells utilizing natural pigments. The list of natural pigments fabricated into solar cells is long, and the sources range from cochineal scale insects, green algae, baker’s yeast, fungi and bacteria to bougainvillea flowers, Chinese medicinal plants (e.g. tea, pomegranate leaves, wormwood, mulberry fruit) and food crops like beets, parsnip, purple cabbage, blackberry and black grapes. The black pigments are of particular interest, including skin melanins providing UV protection and the black powder from cuttlefish (Sepia officinalis) ink sacks. “To maximize the absorption of more photons from the sun light for DSSC,” writes Mbonyiryivuze, “it is better to have a black dye sensitizer having extremely high broadband absorption. It should absorb not only in visible range but also in ultraviolet and near-infrared regions. This challenge can be handled by using natural dyes from other sources such as fauna from which sepia melanin was obtained. Melanins are well-known natural pigments used for the photoprotective role as a skin protector because of their strong UV absorbance and antioxidant properties. Melanin possesses a broad band absorbance in UV and visible range up to infrared.” Sepia melanin “can also conduct electricity and is thus considered a semiconductor material.”

“There are numerous trials of solar cell construction which are based on biomolecules and supramolecular systems, for instance, chlorophylls, porphyrins, phtalocyanines, and other natural or bioinspired dyes,” write researchers in Poland constructing double layer solar cells with cochineal red and gardenia yellow pigments bonded to TiO2 nano-surfaces. “Hybrid materials incorporating biomolecules immobilized on conducting or semiconducting surfaces are unique systems combining collective properties of solids with structural diversity of molecules, which besides photosensitization show other unique electrochemical and catalytical properties.”

According to Mousavi-Kamazani et al. in Material Letters (2015), quantum dots composed of cochineal and copper offer the economically attractive “possibility of single step production of three-layered solar cells.” Clearly, though the distance might be measured in years or decades, we are getting closer to a cochineal and natural pigment renaissance that transcends traditional fabric dyes and artist’s pigments and extends into medicine and the heart of modern computers, lasers and electronic and optical devices of all sorts.

Cholera Biocontrol (vaccines & antibiotics are insufficient)

CHOLERA, a VIRULENT, SOMETIMES lethal version of Montezuma’s Revenge, the diarrheal gut scourge bane of travelers, is commonly associated with pesky Vibrio bacteria; though similar symptoms are associated with the sometimes disease-causing and sometimes beneficial E. coli gut bacterium and many other intestinal tract microbes. Cholera is commonly controlled by an integrated management approach, often including proper sewage sanitation, water filtration, antibiotics, vaccines, rehydration therapy and the fortuitous presence of natural enemies known as phages.

Phages, short for bacteriophages, are ‘bacteria-eating’ viruses; the name phage is from the Greek word ‘phagein’, which means ‘to eat’. One might think of cholera as being like the black plague, a no longer relevant disease of the past. But a recent Google News search indicates lethal cholera outbreaks worldwide: From 54 dead in one month in Dar es Salaam, Tanzania, to Rwanda and Nigeria in Africa to Iraq in the Middle East and Haiti in the Americas; with worries about outbreaks in refugee camps worldwide where wars rage and after natural disasters such as earthquakes destroy sanitary infrastructure. In Iraq, “The epidemic is concentrated in the town of Abu Ghraib, situated about 25 kilometers (15 miles) west of the capital, Baghdad, where cholera has claimed at least 10 lives,” according to Iran’s Press TV. “Health Ministry spokesman Rifaq al-Araji has blamed the cholera epidemic in Iraq on low water levels in the Euphrates, noting that simmering temperatures during summer months may have activated the bacterium that causes the deadly disease…Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It is a fast-developing infection that causes diarrhea, which can quickly lead to severe dehydration and death if treatment is not promptly provided.”

According to a “Major Article” in THE JOURNAL OF INFECTIOUS DISEASES: “Vibrio cholerae serogroup O1 and O139 organisms cause acute, watery diarrhea, with an estimated 100, 000–150, 000 deaths annually…Despite global efforts to improve drinking water quality and sanitation in developing countries, there has been little evidence of a decline in the global burden of cholera in recent years. Interest has therefore increased in the use of cholera vaccines as adjuncts to other preventive and therapeutic measures…Live oral cholera vaccines have the theoretical advantage of simulating infection by natural cholera. Experimental infection of North American volunteers has been shown to protect against cholera upon rechallenge…However, to date no live oral vaccine has conferred protection to cholera-endemic populations when tested in a randomized trial, suggesting that the predictions from studies of volunteers lacking preexisting immunity to cholera may not be readily generalizable to cholera-endemic populations.”

According to the United Nations News Centre: “A global stockpile of vaccines, funded by a number of international organizations and foundations, initially made 2 million doses of the vaccine available. In 2015, with additional funding from the GAVI Alliance, the number of doses available for use in both endemic hotspots and emergency situations is expected to rise to around 3 million. There are several examples in which the vaccine has stopped cholera outbreaks in their tracks, such as in South Sudan in 2014…But new outbreaks are ongoing in South Sudan and Tanzania” in 2015, indicating vaccines to produce natural immunity in conjunction with the best that can be done in the way of sanitation and clean water supplies is not enough. Using phages to produce natural biological control of the cholera bacterium, as part of a low-cost, integrated pest management approach, seems to have been totally and completely neglected, almost as if the successes of natural biocontrol of disease bacteria with phages from the years 1917 into the 1930s and continuing into the present in some parts of the world have been totally purged from the Western medical and public health history books. A costly neglect, in terms of human lives.

“Cholera generated as much horror and revulsion among Europeans as bubonic plague had before it, in part because of the blue-black shriveled appearance of its victims and in part because it could strike anyone without warning and kill in 4 to 6 hours,” according to an overview in Microbiological Reviews which implicated “sailors and colonists” in cholera’s global spread, not just poor sanitation (mixing sewage into drinking water supplies). “Although cholera is treatable with antibiotics and oral rehydration therapy (fluid and electrolyte replacement), it is nevertheless an extremely debilitating and sometimes fatal disease. The severe dehydration and cramps symptomatic of the disease are a consequence of the rapid, extreme loss of fluid and electrolytes during the course of the infection. The diarrhea is caused by the action of cholera toxin (CT), secreted by the bacterium Vibrio cholerae, although in some cases it may be caused by the related Escherichia coli heat-labile enterotoxin (LT).”

Historically, as mentioned in a previous blog post titled “Compost for Sustainable Soil Fertility & Disease Suppression,” Japanese cities adopted a more sustainable approach and thereby escaped the cholera epidemics afflicting London, Paris, India, the rest of Asia and the Americas: “Human waste, euphemistically called night soil, became a valuable soil fertility commodity in old Japan. Perhaps not quite worth its weight in gold, but a valuable commodity bought, sold, traded, and transported long distances from cities to farms. Rather than causing cholera and other diseases by entering the water supply as was common in European cities of the same era, sanitation and composting blessed Japan with multiple dividends…Farmers in old Japan spent their own money to build toilets and urinals along well-traveled roads for public use…” No doubt phages were also part of the integrated mix of methods providing natural biological control of cholera in old Japan, even if the invisibly small phages went unrecognized.

The 20th century use of phages for biological control of cholera and other disease bacteria was pioneered by the self-taught, French-Canadian microbiologist Felix d’Herelle, whose phage work was said by many to also be the foundation for modern molecular biology. An itinerant or journeyman scientist, who spent his life much like the modern-day post-doc, migrating from job to job around the world as he promoted phage therapy, d’Herelle was working with the Pasteur Institute in Paris while French and German troops were lining up against each other on the Western Front in World War I. In North Africa, as early as 1910, d’Herelle was pioneering the use of microbes to control biblical style locust plagues in North Africa, when he first noticed something killing the microbes used to kill the locusts; in other words, a complex ecosystem in which a higher level of natural enemies killed the lower-level natural enemies providing biological locust control.

During a World War I Paris dysentery outbreak, d’Herelle deduced that some patients were benefiting from phages invisibly providing biological control of the disease microbes. D’Herelle’s 1917 article on the subject for the French Academie des Sciences was titled “Sur un microbe invisible antagonistic des bacilles dysenterique” (“On an Invisible Microbe Antagonistic to Dysentery Bacteria”). “D’Herelle claimed that the antagonistic principle was filterable, living and organized, and hence a microbe,” wrote medical historian Ton Van Helvoort. D’Herelle “thought the living nature of the principle was proved by the possibility of transmitting it in a series of cultures of dysentery bacilli.”

Albert Einstein, who won a Nobel Prize for proving unseen forces and counter-intuitive phenomena based on mathematical constructs, agreed with d’Herelle. “The statistical explanation, which d’Herelle argued intuitively, is based on the properties of sampling that can be described by the mathematical expression known as the Poisson distribution,” wrote William Summers in his book, Felix d’Herelle and the Origins of Molecular Biology. “D’Herelle bolstered not only this argument but his own status with his well-known footnote giving Einstein’s opinion of this experiment: ‘In discussing this question with my colleague, Professor Einstein, he told me, as a physicist, he would consider this experiment as demonstrating the discontinuity of the bacteriophage. I was very glad to see how this deservedly-famous mathematician evaluated my experimental demonstration, for I do not believe that there are a great many biological experiments whose nature satisfies a physicist’…Since we have now presented the evidence proving the corpuscular nature of the bacteriophage we will no longer make use of such vague expressions as bacteriophage ‘liquid,’ ‘Fluid,’ or ‘filtrate,’ but will employ instead the more precise term’…The validity of the plaque counting assay and corpuscular nature of phage, however, would remain controversial and divide phage workers into two camps until the early 1940s.”

“The bacteriophage phenomenon was the observation that an abundant and therefore cloudy bacterial culture lysed within a short time to a clear solution under the influence of a filterable lytic ‘principle’,” wrote medical historian Ton van Helvoort. “The interpretation of this phenomenon gave rise to two main opposing positions, represented by Felix d’Herelle and Jules Bordet, who clashed heavily. In 1917, d’Herelle proposed the term “bacteriophage” for the lytic principle and was convinced it was to be characterized as a filterable virus which could lyse the bacterial culture. Therefore, this lysis was a virus disease of the bacteria which he named bacteriophagy. In the 1920s this interpretation was severely criticized by, among others, the bacteriologist and serologist Jules Bordet, who received the Nobel Prize for Medicine in 1919. Bordet’s view was that bacteriophagy was linked with the metabolism of the bacterium, while the involvement of a virus was rejected.” The dispute morphed into a personal vendetta against d’Herelle, whose strong personality was perhaps hated as much as his phage theories and his views on the dangers of vaccination that were considered heretical by the era’s Nobel Prize-winning immunologists.

According to medical historian Dottore Emiliano Fruciano: “In presenting his concepts to the scientific and world community, d’Herelle connected his phage interventions to a theoretical system that clashed with those held by institutional medical science. d’Herelle thought that the reason for natural recovery was not the humoral and cellular mechanisms activated by the immune system, but rather the presence of a virulent phage for the pathogenic bacterium in the host. His observations led him to believe that phage was a common guest of every organism from man to silkworm…d’Herelle concluded that phage was the exogenous agent of natural recovery, leading to ‘spontaneous recovery’…

“Recovery was a case of the prevalence of phage over the bacterium, and death was a case of the prevalence of bacterium over phage,” wrote Fruciano. “Furthermore, d’Herelle hypothesized that phage was able to spread among ill people, mainly via stool; thus, a lack of hygiene, while contributing to infection, would also lead to recovery; phage would have been the reason for the end of epidemics. This characteristic made phage, the recovery agent, transmissible between individuals, just like the agent of disease…

“In support of his theory of natural recovery, d’Herelle cited exemplary phenomena, including recovery following exposure to cholera. In cholera, patients generally convalesced after two or three days (sometimes within 12 hours) of initial symptoms; even ‘artificial’ recoveries through phage therapy often occurred after 24 hours. However, according to d’Herelle, observations from many animal diseases had demonstrated that it took many more days for immunity to become effective in the fight against infection. To explain natural recovery through the mechanisms of immunity was not possible because of the timing.

“Moreover, in diseases such as typhus and plague, which are characterized by strong immunity, relapses were possible during convalescence. This would mean that the patient, although convalescing, was still not immune. In these kinds of pathologies, typically typhus and plague, immunity usually lasts forever, yet immunity only comes into play 20 days following convalescence. According to d’Herelle, ‘Immunity, far from being the cause of recovery, is a consequence of recovery’. Further confirmation of d’Herelle’s theory was given by the statistics of the three hospitals in Calcutta, India. Paradoxically, the lowest rate of mortality for cholera (27%) was recorded at the hospital for poor people, the Campbell Hospital, while the highest rate of mortality (86%) was recorded at a hospital for rich people, the European Hospital – a hospital recognized in 1926 for its wealthy patients and hygienic conditions. There were fewer deaths at the hospital where care and hygiene were poor, that is, where the possibility for the development and dissemination of virulent phage or the recovery agent were best.”

The cholera and phage biocontrol case in general became intolerably heretical to many in the scientific medical establishment, what with d’Herelle’s warnings against the dangers of conventional vaccinations and the radical challenge to conventional consensus medical theories supported by immunologists who had won Nobel Prizes in medicine, said Fruciano: “According to d’Herelle, immunity and recovery were two different processes; only after the bacteriolytic action of phage could immunity be developed. Furthermore, there were two kinds of immunity: heterologous immunity, linked to the presence of phage activity against the pathogen, and homologous immunity, linked to immune system activity.

“…man contracts cholera because his immune system is not able to neutralize the bacterium. In d’Herelle’s opinion, in the case of patients with cholera, recovery occurs because of the presence of a virulent phage for Vibrio cholerae as a result of heterologous immunity, not because of natural or homologous immunity. d’Herelle found that the administration of phage resulted not only in a quick recovery, but also lasting immunity. He also asserted that a suspension of phage had strong immunizing power (here in the traditional sense) because the bacterial substances dissolved by phage action induced immune system reactions… d’Herelle’s findings were contrary to the conclusions of Metchnikoff, Bordet and Ehrlich, the founders of immunology…phage therapy efficacy would have required a revision of the current explanation of natural recovery…In other words, the proof of efficacy of phage therapy was equivalent to the proof of the truthfulness of d’Herelle’s heretical theories. Thus, to verify the efficacy of phage therapy and prevention measures, the principles of modern medicine were at stake; this was a paradigm shift for the scientific community.”

Of course, in the early years of the 20th century, prior to the invention of the electron microscope to provide visual evidence, the immunologists could plausibly argue against the existence of phages (despite Einstein’s endorsement); and in the absence of modern genomics, indeed before DNA and RNA were implicated in heredity, matching the right mixture of phages with a particular disease bacterium was perhaps more art than science, an art in continuous successful practice in just a few places such as the ex-Soviet Republics of Georgia and Russia, and Poland. Also, early 20th century medical experiments are not considered rigorous by current standards. All of which makes the several hundred successful phage experiments and interventions against cholera, plague, typhus and other diseases subject to blanket dismissal; and, hence, the absence of natural biological control from Western medical practices, medical schools, and institutional research agendas.

“The following details some of the most sensational results in phage prophylaxis that would seem to contradict the eventual dismissal of d’Herelle’s works,” stated Fruciano. “In 1927, an epidemic of Asiatic cholera was halted at its start in several villages with 2000 to 3000 Punjabi inhabitants via two methods of phage prophylaxis delivery: the first was the addition of potent, individually dosed phage preparations, and the second was the administration of phage prophylaxis to local water supplies. In both scenarios, the epidemic was terminated within 48 hours; in the past, the same result was achieved through traditional interventions within a 26-day time period.

“…at the St Mary Hospital in London, England, where penicillin was first discovered, Himmelweit developed a cross-therapy involving a combination of phage and penicillin to reduce the possibility of penicillin-resistant bacteria. This solution was very promising…Above all, the conjoined administration of phage and penicillin gave positive outcomes in clinical trials. It is likely that this experimental solution worked well because, as it is known today, the mechanisms by which phage and penicillin kill bacteria are different. Unfortunately, this alternative use of phage, in combination with penicillin, has been abandoned. Why has this possibility been forgotten despite the fact that antibiotic-resistant bacteria appeared as soon as penicillin was introduced into medical practice?

“…Summers, a historian of medicine who delved deeply into d’Herelle’s scientific works, speaks of the “Soviet Taint” as a plausible reason for the lack of interest in phage as an antimicrobial agent. Following World War II, phage therapy research continued only in eastern European countries, and “d’Herelle’s Cure” became “Stalin’s Cure”. According to Summers, phage therapy and prophylactic measures became ideological symbols of divisions and disagreements between western and eastern countries, partially explaining the lack of interest in phage as an antibacterial agent in Western medical science.”