Today, Memorial Day 2024, we pay tribute our fallen soldiers, and those who served, survived, and struggled home.

It's a day I remember my American Revolutionary War ancestors, but especially my Civil War ancestor, Samuel Davidson Laughlin, who at age 18 served as a Union color bearer in the Civil War. He was selected to carry Old Glory for his height (6'3"), his strength (farm boy from Linn, Mo.) and his courage (front-line duty).

"Being a color bearer (aka carrying the flag), was a prestigious and important role in the Army. Not only were you carrying the symbol of what you were fighting for, the flag was any easy mark for soldiers to organize around," according to an article written in a National Museum of Civil War Medicine post by Amelia Grabowski, the outreach and education coordinator at the National Museum of Civil War Medicine and the Clara Barton Missing Soldiers Office Museum.   

Young Samuel carried the flag in three of the bloodiest battles of the Civil War: the Battle of Lookout Mountain, and the battles of Chicamauga and Chattanooga. A musket tore a hole in his flag but he emerged from the Civil War physically unscathed.

He returned home to Missouri, married, moved with his family to Castle Rock, Wash., and built a round barn there in 1883. He would die of blood poisoning in 1910. In 1986 his barn would be listed in the National Register of Historic Places.  

He rests in a small cemetery next to his beloved barn. His gravestone reads simply: "Gone, But Not Forgotten."

"Color bearer" Noah Coughlan, a native of Vacaville, Calif., paid tribute to American soldiers, including Samuel Laughlin, in his 2023 Run Across America that spanned 167 days and 3,600 miles.  See Run for Revival. 

In addition, Memorial Day traditionally marks the beginning of summer, and as an aside, it's often the weekend when we see our first monarch of the year. Yesterday, right on cue, a monarch fluttered through our garden,  touched down on a cherry laurel branch,surveyed the milkweed and floral resources, and then, poof...gone.

But not forgotten. 

Monarchs and California golden poppies...Color them orange...Color them bold...Color them beautiful...

And color them natives...

The California golden poppy, Eschscholzia californica, California's state flower, is popping up all over, while monarchs, Danaus plexippus, are winging their way inland from their overwintering sites along the California coast.

The overwintering population in California dropped this year by 30 percent as compared to last year, according to the Xerces Society for Invertebrate Conservation. The stormy weather didn't help.

"The 27th annual Thanksgiving count ran from November 11 through December 3, 2023, totaling 233,394 butterflies across 256 overwintering sites in the western United States," Xerces reports on its website. "This tally is slightly lower than last year's (330,000), yet similar to the 2021 count. The overwintering population of western monarchs remains at approximately 5% of its size in the 1980s."

Overall, habitat loss and increased use of pesticides and herbicides continue to be key factors in the decline of the monarch population.

Interestingly enough, both monarchs and California golden poppies are toxic. "All parts of the (California golden poppy) plant have toxic properties if ingested," according to the State of California Capitol Museum website. And, as we all know, monarchs are toxic. As caterpillars, monarchs sequester or store toxins from milkweed, and those toxins help protect them from predators. The coloring is also a deterrent. 

Two natives, toxic, but beautiful...

Good news!

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.”

Initial results of the first cohort, completed in December 2023, showed no significant adverse effects in any of the subjects. Each took a 4-milligram (mg) loading dose on Day 1 followed by a daily 2-mg maintenance dose for six consecutive days. The second cohort (8-mg loading dose on Day 1 followed by daily 4-mg maintenance dose for an additional six days) will be initiated in January 2024.

“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.”

"The safety study of EC5026 in healthy human subjects is a crucial step in the development of of this designer inhibitor of soluble hydrolase for treating Parkinson's disease,” said neurologist and UC Davis School of Medicine (SOM) professor Dr. Lin Zhang, director of the UC Davis Center for Movement Disorders and Neuromodulation, a Parkinson's Foundation Center of Excellence based in the SOM Department of Neurology; and interim chief of the Movement Disorders Section, Department of Neurology.

“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 National Institutes of Health (NIH) supported the progression of EC5026 into clinical trials through the Blueprint Neurotherapeutics Network for Biologics (BPN; grant number UH3NS094258-02), and the Helping to End Addiction Long-term Initiative (NIH HEAL Initiative) to replace addictive opioid pain relievers.

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.

They crawl, they fly, they flutter, they buzz.

They look at us, and we look back.

But if you're Larry Snyder of Davis, an insect photographer and a retired musician, you not only look back, but you take their images.

Snyder does just that when he observes the insects at the city-owned North Davis Channel, the site of a former monarch-milkweed research project organized and directed by UC Davis professor Louie Yang. The site is also known as "the Covell drainage channel."

And now Snyder is sharing many of his images in a photography exhibit, "Insects at the Ditch," which opened Jan. 6 and continues through Feb. 2 at Logos Books, 513 2nd St., Davis.

The UC Davis research project began in December 2013 when Yang, a community ecologist, and his team planted narrow-leaved Asclepias fascicularis, at the site.  Then they monitored the interactions of the monarchs, Danaus plexippus, on the plants from 2015 through 2017, culminating in the July 2022 publication of "Different Factors Limit Early-and Late-Season Windows of Opportunity for Monarch Development," in the journal Ecology and Evolution.

"I began watching, and then photographing, the insect life on the plants," Snyder related, adding that he became especially interested in insect behavior and interaction.

"It's my adopted back yard."

Snyder captured the images with a Sony α7r iii digital camera and a manual-focus Voigtlander 110mm macro lens, handheld in natural light. 

"I am grateful to the Bohart Museum of Entomology and its remarkable staff and associates for the frequent assistance in identification and understanding of life in the insect world." He has also shared his images with the Bohart Museum. 

Snyder, a retired harpsichord maker, piano technician, and music instructor, is a 1968 alumnus of UC Davis, with a degree in English literature. He worked as an apprentice in Boston before returning to California. He founded and directed  the Mosswood Spring Opera "for the purpose of giving younger, less experienced singers the chance to perform roles opposite others who had sung in larger companies."

He directed the opera from 1976 to 2000. He also published a book, German Poetry in Song, in 1995.  In 2001 he chaired the organizing committee for The Davis Star Show astronomy festival.

Snyder's last photography show (of 5x7 black and white contact prints) was at the old Davis Art Center in 1985. He recalls using a "5x7 Deardorff, one of those things resembling an accordion on stilts, rather unsuited for living macro subjects, and which I sold 25 years ago."

As the late E. O. Wilson said: "It's the little things that run the world."

(Editor's Note:  The Bohart Museum, home of a global collection of eight million insects, is located in Room 1123 of the Academic Surge Building, 455 Crocker Lane, UC Davis. The Bohart Museum's next open house, themed "Social Wasps,"  is from 1 to 4 p.m., Saturday, Jan. 20. It is free and family friendly.  UC Davis distinguished professor Lynn Kimsey, director of the Bohart, will share her wasp expertise.)