- Author: Kathy Keatley Garvey
Monarch butterflies seem to be as scarce as hen's teeth around here.
And since hens have no teeth, that's pretty scarce.
And then it happened.
A late in-star monarch caterpillar appeared on our milkweed in our Vacaville pollinator-predator garden on the very last day of July.
We watched it munch the wilting milkweed leaves in the triple-digit temperature.
For one day.
The next day, Aug. 1, it vanished, never to be seen again. Did it pupate? Did the California scrub jays get it?
The scrub jays nesting in our cherry laurel hedges are prime suspects. They devour everything in the garden, from honey bees, longhorned bees and dragonflies to assorted butterflies, lygus bugs and praying mantises. Happy meals. If they eat a monarch caterpillar, that makes for an unhappy meal, the vomiting kind. It's about the naturally occurring toxins (cardiac glycosides) in the milkweed that the 'cats ingest that serve as predatory protection. That's why scientists say "I bet you'll eat only one."
Just one. The one we were watching?
"Known bird predators include brown thrashers, grackles, robins, cardinals, sparrows, scrub jays and pinyon jays," Wikipedia says, but notes that "Several species of birds have acquired methods that allow them to ingest monarchs without experiencing the ill effects associated with the cardiac glycosides (cardenolides). The black-backed oriole is able to eat the monarch through an exaptation of its feeding behavior that gives it the ability to identify cardenolides by taste and reject them. The black-headed grosbeak, though, has developed an insensitivity to secondary plant poisons that allows it to ingest monarchs without vomiting. As a result, these orioles and grosbeaks periodically have high levels of cardenolides in their bodies, and they are forced to go on periods of reduced monarch consumption. This cycle effectively reduces potential predation of monarchs by 50% and indicates that monarch aposematism has a legitimate purpose. The black-headed grosbeak has also evolved resistance mutations in the molecular target of the heart poisons, the sodium pump. The specific mutations that evolved in one of the grosbeak's four copies of the sodium pump gene are the same as those found in some rodents that have also evolved to resist cardiac glycosides."
- Author: Kathy Keatley Garvey
EicOsis Human Health LLC, the Davis-based pharmaceutical company developing a non-narcotic drug to relieve chronic pain and inflammation, today announced the next step in its ongoing human clinical trials: the initiation of Phase 1b to test the safety of its drug candidate, EC5026.
The ongoing double-blind, placebo-controlled Phase 1b study is designed to investigate the safety and pharmacokinetics of daily doses of EC5026 over seven days.
EC5026, an inhibitor of the soluble hydrolase enzyme (sEH), was discovered and patented at EicOsis based on previous patents and research papers from the laboratory of UC Davis distinguished professor Bruce Hammock during his half-century of research.
“EC5026 plays a crucial role in regulating the metabolism of signaling lipids and responding to inflammation and other stress responses caused by trauma or disease,” said Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “We found sEH to be a target for treating pain, inflammation, cancer and other diseases.”
By inhibiting sEH, EC5026 alleviates pain by preventing the breakdown of natural analgesic and anti-inflammatory fatty acids. Preclinical studies demonstrate no sedation or other adverse behavioral effects and no signs of addiction.
“Many regulatory molecules are controlled as much by degradation as biosynthesis,” Hammock explained. "The epoxy fatty acids rapidly degraded by the sEH control blood pressure, fibrosis,immunity, tissue growth, depression, pain, and inflammation, to name a few processes.”
“The initial results from Cohort 1 appear to replicate the very favorable safety profile we observed in our previous two Phase 1a clinical studies where there were no adverse behavioral, cardiovascular, or neurological effects over five ascending single-dose levels,” said Dr. William Schmidt, EicOsis vice president of clinical development. “The maximum dose level was 5 to 10-fold higher than the anticipated analgesic dose in humans.”
“If Cohort 2 dosing also proceeds without clinically significant adverse effects and a favorable pharmacokinetic profile for once-a-day dosing,” Schmidt continued, “this provides encouragement for initiating our first analgesic efficacy study in the second quarter of 2024.”
EicOsis plans to initiate its first pain patient study in April 2024 “to evaluate safety and analgesic effects in patients with a spinal cord injury who have failed to achieve satisfactory pain relief with existing non-opioid chronic pain medications,” said Cindy McReynolds, EicOsis chief executive officer and former director of research.
“Initiation of the Phase 1b program represents a significant milestone for EicOsis Human Health and demonstrates the success and dedication of our team to make this happen,” said McReynolds, who holds a doctorate in pharmacology and toxicology from UC Davis. “Demonstrating safety in Phase 1b studies will allow us to evaluate efficacy in patients and bring forward safe and effective treatments for several serious diseases. For example, the sEH inhibitors are being considered for use for treatment of cancer in the UC Davis Comprehensive Cancer Center, and neurological disease through the UC Davis Health's designated Parkinson's Foundation Center of Excellence.”
“As a potential anti-inflammatory fatty acid, EC5026 holds promise in addressing neuroinflammation, a key factor in the manifestation and even progression of Parkinson's,” said Zhang, who holds both an M.D. and a PhD. “Ensuring its safety profile in healthy individuals is fundamental for establishing a foundation for further clinical trials. this investigation provides valuable insights into design and overall safety parameters, paving the way for the next stages in advancing this innovative therapeutic approach for Parkinson's disease."
The FDA granted Fast Track status to EC5026 in April 2020 to support the unmet medical need for safe and effective non-opioid analgesics. EicOsis clinical scientist Irene Cortés Puch, who authored the successful application, commented: “Both our commitment and focus at EicOsis Human Health are guided by a genuine concern for the well-being of patients and recognizing the importance of identifying effective pain management alternatives. Therefore, the initiation of this Phase 1b clinical trial is an exciting step in advancing our mission to provide safer and effective treatments.”
Hammock traces his research on chronic pain to his earlier work on how a caterpillar becomes a butterfly; a key enzyme, epoxide hydrolase, degrades a caterpillar's juvenile hormone, resulting in metamorphosis.
A member of the UC Davis faculty since 1980, Hammock founded ;EicOsis in 2011 and served as its chief executive officer until February 2023 when he transitioned to scientific officer and chairman of the board of directors. Highly honored by his peers, he is a member of the National Academy of Inventors and the National Academy of Sciences and received the 2020 Lifetime Achievement Award in Innovation from UC Davis Chancellor Gary May. Hammock has authored or co-authored more than 1400 peer-reviewed publications and holds more than 95 patents in agriculture, environmental science and medicinal chemistry.
EicOsis (pronounced eye-co-sis), derives its name from eicosanoids, “the major backbone of chemical mediators in the arachidonate cascade,” McReynolds said. “It symbolizes the epoxide group in chemistry, which is key to the anti-inflammatory chemical mediators and where the biochemical target called soluble epoxide hydrolase works.”
Approximately 50 million Americans (20 percent of the population) suffer from chronic pain, according to the Centers for Disease Control and Prevention. The annual economic toll is $560 billion, encompassing direct medical expenses, lost productivity, and disability claims.
More information on the Phase 1b multiple-ascending dose clinical study is available at https://clinicaltrials.gov/study/NCT06089837.
- Author: Kathy Keatley Garvey
The third instar monarch caterpillar we found munching on the remnants of our cut-back milkweed on Jan. 23 in Vacaville, Calif., is now an adult butterfly fluttering around the neighborhood.
We brought the caterpillar in from the bitter cold and heavy rain and reared it in our Bohart Museum of Entomology habitat. Did it like the kitchen? The coffee brewing, the dishes rattling, and NPR sharing information on the declining monarch population?
A strange new world, for sure. But there it was safe and sound. Well, apparently sound.
It pupated on Feb. 4, forming a spectacular jade green chrysalis. Then we waited. And waited. And waited some more. It usually takes 10 to 14 days for a monarch to eclose but this one took 20 days.
We could see our little buddy's iconic orange wings through the transparent chrysalis. We joked about having a gender revealing party. Male? Female?
Finally, on Feb. 24, a healthy male eclosed. We don't usually name the monarchs we rear, but this one we named "Perseverance" after NASA's 2020 Perseverance rover looking for signs of life on Mars.
We released Perseverance on Feb. 25 on an abnormal spring-like day. For 10 minutes, he warmed his wings. Then he fluttered away as if he knew where he was going and what he was going to do when he got there. Monarchs are like that.
"Safe travels, Perseverance," we called after him.
In a previous Bug Squad blog, we likened our "winter monarch caterpillar find" to seeing the Easter Bunny delivering candy in December or Santa Claus handing out candy canes on Easter Sunday.
"Mama Monarch" must have laid the egg in late December, surmised butterfly guru Art Shapiro, UC Davis distinguished professor of evolution and ecology, who has researched butterfly population trends since 1972 and maintains a research website, Art's Butterfly World. "Evidence of inland winter breeding," he commented. "Nothing surprises me any more..." Indeed, he saw and recorded a monarch in Sacramento on Jan. 29, 2020.
In 2020, we collected more than 300 monarch eggs or caterpillars in our pollinator garden, primarily from two of the three milkweed species. We reared and released them or donated them to researchers at the University of California, Davis and the University of Nevada to start their own colonies.
The magical metamorphosis, the incredible transformation from egg to caterpillar to chrysalis to adult, never ceases to amaze. Neither does the Chuang Tzu philosophy: "Just when the caterpillar thought the world was over, she became a butterfly."
Just when Perseverance thought the world was over, he became a butterfly.
Maybe he will meet up with that monarch was saw Feb. 23--23 miles away in Benicia.
- Author: Kathy Keatley Garvey
The monarch caterpillar feasting on the tropical milkweed, Asclepias curassavica, in Vacaville, Calif., kept doing what monarch 'cats do best--eat.
She insisted on devouring the leaves as if there were no tomorrow--and today would end soon.
How did we know her gender? Our Danaus plexippus pupated, formed a chrysalis, and emerged. Oh, you beautiful gal!
Folks who comment that someone is "eating like a pig" or "eating like a horse" or "wolfing it down," have probably never seen a monarch caterpillar chow down, scarf it up or shovel it in.
One minute our little 'cat is stretched out on a leaf, binge eating. The next minute the leaf is gone and she's porking out on a second leaf. And scouting for a third.
Eric Carle titled his classic children's book, "The Very Hungry Caterpillar," quite well. His little 'cat ate everything in sight: gobbling, guzzling, gorging and gulping down everything from fruits and vegetables to junk food.
Remember the story? First, the little 'cat ate an apple, two pears, three plums, four strawberries, and five oranges but was still hungry. Famished, really. So he ate a piece of chocolate cake, a lollipop, a piece of cherry pie and a cupcake...and more...and he wasn't little anymore.
Many folks sheltering at home during the COVID-19 crisis can certainly identify with the snatch-and-grab menu of "The Very Hungry Caterpillar."
Did someone say "chocolate cake?"
(Editor's Note: Those planting the tropical milkweed in temperate zones (like here in Vacaville,Calif.) must remove or cut back the tropical milkweed by winter. "A protozoan parasite of monarch butterflies, Ophryocystis elektroscirrha or OE for short, can travel with monarchs visiting the plants and become deposited on leaves," explains the Xerces Society for Invertebrate Conservation.)
- Author: Kathy Keatley Garvey
Picture this during National Pollinator Week: five monarch caterpillars and assorted honey bees sharing tropical milkweed.
It was love at first bite. Or love at first sip.
The 'cats kept munching and the bees kept foraging. Neither species seemed interested in the other.
But the adult monarchs definitely showed more interest in the tropical milkweed (Asclepias curassavica), a non-native, than the other two species, both natives, that we planted: the narrow leaf (A. fascicularis) and showy milkweed (A. speciosa).
They laid eggs only on the tropical milkweed, and so far, have produced five caterpillars.
The score to date:
Tropical milkweed: 5 caterpillars
Narrow leaf milkweed: 0
Showy milkweed: 0
Reminder: Folks planting the tropical milkweed in temperate zones (like here in Vacaville,Calif.) must remove or cut back the tropical milkweed by winter. "A protozoan parasite of monarch butterflies, Ophryocystis elektroscirrha or OE for short, can travel with monarchs visiting the plants and become deposited on leaves," explains the Xerces Society for Invertebrate Conservation.
Yes, indeed. But meanwhile, we're witnessing untold sharing on the wildly popular tropical milkweed by not only monarch caterpillars but honey bees, syrphid flies, bumble bees, carpenter bees, leafcutter bees and sweat bees.
We gardeners and photographers are also drawn to the spectacular red, orange and yellow flowers that add both beauty and color to a cherished pollinator patch in the midst of the COVID-19 pandemic...and National Pollinator Week.