Born Jan. 30, 1951 in Hong Kong and fondly known as “Amazing Grace,” she received her doctorate at UC Davis in 1983 with major professor Hammock, now a UC Davis distinguished professor who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center.
Her husband of 41 years, Davy Jones, a longtime professor in the UK Department of Toxicology and Cancer Biology, received his doctorate from UC Davis, studying with major professor Jeffrey Granett of the then Department of Entomology.
Hammock described Grace Jones as a hard-working scientist with “amazing skill and creative insight.”
“Following her research at Texas A&M University, Grace joined my lab in the 1970s at UC Riverside and then finished her PhD at Davis in 1983,” recalled Hammock, a member of the UC Riverside faculty from 1975 to 1980, when he accepted a joint-faculty appointment in toxicology and entomology at UC Davis.
“She asked how juvenile hormone regulated the development of moth larvae that are serious agricultural pests,” Hammock said. “She also found two parasites, one of which sped up host larval development and the other of which slowed host larval development. She found that both parasitoids were manipulating the host insect endocrine system to their benefit. Endocrine regulation of insect development was a theme of Grace's whole career which she pursued with amazing skill, hard work and creative insight.”
Longtime friend and colleague Lynn Riddiford, emerita professor of biology at the University of Washington, Seattle, who worked with Grace Jones on a National Science Foundation grant, praised her as “a creative and imaginative scientist.”
“Her research focused on the action of juvenile hormone (JH), a key hormone regulating metamorphosis in insects,” Riddiford said. “Early on Grace studied the molecular mechanisms involved in the regulation by JH of several proteins in the cabbage looper, Trichoplusia ni—the JH-inducible JH esterase that breaks down JH and several JH-suppressible hemolymph storage proteins. Her work was always careful and thorough and contributed significantly to the field.”
Riddiford said that “Grace became intrigued by the idea that Ultraspiracle (USP), the heterodimeric partner of the ecdysone receptor (EcR), might be the long-sought JH receptor. She pursued this line of research with rigor, and later found that USP bound methyl farnesoate, the immediate precursor of JH, with the high affinity typical for hormone receptors. Furthermore, she showed that the methyl farnesoate-USP complex was critical for the larval-pupal transformation in Drosophila. Even though her initial idea that USP was the JH receptor proved wrong, her work stimulated the field and resulted in a deeper understanding of the factors controlling metamorphosis in Drosophila.”
Riddiford added: “Grace will be especially remembered for her amazing drive and determination to forge ahead with her science and to continue to make significant contributions despite the disabilities engendered by her stroke.” (See research publications)
Keith Wing, Hammock's second doctoral student who went on to become a senior research associate at Rohm and Haas and DuPont, and is now a consultant, remembered her as “a cheerful, hard-working colleague and friend, and wife of Dr. Davy Jones, University of Kentucky. A few of us spent many a late night studying juvenile hormone esterase and binding proteins at UC Riverside and Davis in lepidopteran larvae, trying to help the lab piece together the story of how JH metabolism and transport helped to regulate insect metamorphosis.”
“We shared everything and always helped each other out,” Wing said. “Grace went on to focus on this in much greater detail, including exploration into insect hormone receptors and regulation. She was an incredibly dedicated researcher who contributed a lot to the field."
Grace Jones received her bachelor's degree in biology in 1973 from Belmont (N.C.) Abbey College, and her master's degree in biology in 1974 from Jacksonville (Ala.) State University. She did post graduate research at Texas A&M in insect physiology and endocrinology before joining the Hammock lab in UC Riverside (1979-80). After receiving her doctorate in 1983 from UC Davis, she headed to Harvard University's Medical School as a visiting scholar in the Department of Cell Biology and Department of Pathology, working there from 1989 to 2000. Her career then included visiting scientist at Massachusetts Institute of Technology's Department of Biology and a visiting professor at Baylor College of Medicine, where she specialized in stem cell research.
The UC Davis alumnus joined the UK Department of Entomology in 1984 as an assistant research professor, studying insect biochemistry and molecular biology. She was promoted to associate research professor in 1990, and then switched to UK's School of Biological Sciences, becoming an assistant professor of molecular and cellular biology in 1991; an associate professor in 1993; and a full professor in 1999.
"Dr. Jones was a superb, internationally recognized scientist, even as her health declined over the past 18 years, but she continued to work on teaching and research throughout," wrote UK Department of Biology chair Vincent Cassone on a web page memoralizing her. "Over the course of her research career, Dr. Jones had received millions of grant dollars for her important studies from the National Institutes of Health and National Science Foundation, and published more than 100 research articles in prestigious journals such as the Proceedings of the National Academy of Sciences, USA, Journal of Biological Chemistry, and Molecular and Cellular Endocrinology. She and Davy also received a patent in 2007 for a method to identify drugs that interact with insect nuclear receptors, which could be used for biological control of pest species."
"Over the years, students have expressed great admiration and love for Professor Jones in letters and emails, and eminent scientists have expressed their high regard for her work," Cassone wrote. "A Grace Jones Memorial Fund for Family Support has been set up. Donations can be sent to the UK College of Health Science c/o Loralyn Cecil, 900 South Limestone 124E, Lexington, KY 40508 or online at https://karrn.org/. Her infectious smile will be missed in the halls of Biology, as she had her daily walks, arm in arm, color-coordinated with her husband, Davy, a testament to devotion and love."
Davy Jones notified his wife's friends and colleagues, including Hammock, of her death with an email, “Butterfly has flown on.” He attached a photo of Grace and a blue morpho butterfly.
She died in his arms, as this song, “Amazing Grace,” played softly in the room, he wrote.
“UC Riverside, UC Davis and the field lost a wonderful colleague and we have all lost a dear friend,” Hammock told him.
Now, newly published research on ovarian cancer, involving an anti-inflammatory compound discovered and developed in the Bruce Hammock lab at the University of California, Davis, and tested at Harvard Medical School on mice models, indicates that the compound not only suppresses inflammation but reduces cancer growth, acting as a “surge protector.”
“We are excited about this research and its potential,” said Hammock, a UC Davis distinguished professor who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “Chemotherapy and surgery, the mainstays of conventional cancer treatment, can act as double-edged swords. It is tragic that the very treatments used to cure cancer are helping it to survive and grow.”
The research is a “novel approach to suppressing therapy-induced tumor growth and recurrence,” said the 13-member team from Harvard Medical School/Beth Israel Deaconess Medical Center (BIDMC), UC Davis, Institute of Systems Biology of Seattle, and Emory University School of Medicine of Atlanta.
Their paper, “Suppression of Chemotherapy-induced Cytokine/Lipid Mediator Surge and Ovarian Cancer by a Dual Cox-2, sEH Inhibitor,” appears today in the Proceedings of the National Academy of Sciences (PNAS).
“To prevent tumor-recurrence after therapy, it will be critical to neutralize the inherent tumor-promoting activity of therapy-generated debris,” said lead author Allison Gartung of Harvard Medical School/BIDMC. “Our results indicate that a dual COX-2/sEH inhibitor may offer a novel alternative to protect the body from a debris-mediated inflammatory response.”
Gartung said that the study confirmed that chemotherapy-killed ovarian cancer cells “induce surrounding immune cells called macrophages to release a surge of cytokines and lipid mediators that create an optimal environment for tumors to survive and grow.”
The team treated the mice models with a dual lipid pathway inhibitor discovered several years ago in the Hammock lab. It integrates two anti-inflammatory drugs (COX-2 inhibitor and soluble expoxide hydrolase (sEH) inhibitor) into a single molecule with the aim of reducing tumor angiogenesis and metastasis.
Chemist Sung Hee Hwang of the Hammock lab developed the compound, known as PTUPB, for the study. “The dual inhibitor here follows earlier work we did with it, blocking breast and lung tumors in mice,” Hammock said. “PTUPB is already being clinically evaluated for its therapeutic properties in other diseases.” Chemist Jun Yang of the Hammock lab did the mass spectrometry, showing how stabilization of lipid mediators reduces cancer growth and metastasis.
Lead researcher Dipak Panigrahy, a former Harvard physician turned full-time researcher, described chemotherapy and surgery “as our best tools for front-line cancer therapy, but chemotherapy and surgery create cell debris that can stimulate inflammation, angiogenesis, and metastasis. Thus, the very treatment used by oncologists to try to cure cancer is also helping it survive and grow. Overcoming the dilemma of debris-induced tumor progression is critical if we are to prevent tumor recurrence of treatment-resistance tumors which lead to cancer therapy failure.”
The tumor cell debris generates a “cytokine surge” that can result in a perfect storm for cancer progression. “The dual inhibitor acts as a surge protector,” Panigrahy said.
Panigrahy, who led angiogenesis and cancer animal modeling in the laboratory of Judah Folkman, a leading cancer research laboratory, based the debris model on his mother's chemotherapy treatments, and dedicated the research to his mother and “all other women who lost their lives to ovarian cancer.” American Cancer Society statistics show that among women, ovarian cancer ranks fifth in cancer deaths. A woman's risk of ovarian cancer is about 1 in 78; every year more than 14,000 die from the disease.
“Traditional cancer therapy sets up a dilemma,” Panigrahy commented. “Yes, we need to kill cancer cells but the inevitable byproduct of successfully doing so also stimulates tumor regrowth and progression. The more tumor cells you kill, the more inflammation you create, which can inadvertently stimulate the growth of surviving tumor cells. Overcoming the dilemma of debris-induced tumor progression is paramount if we are to prevent tumor recurrence of treatment-resistant tumors – the major reason for failure of cancer therapy. Our studies potentially pave the path for a new strategy for the prevention and treatment of chemotherapy-induced resistance with potential to translate to the clinic. If successful, this approach may also allow us to reduce the toxic activity of current treatment regimens.”
“The collaborative work in this paper not only defines a common problem with current cancer therapy, but it actually offers a potential solution to reduce metastasis and tumor growth following therapy,” said Primo Lara Jr., director of the UC Davis Comprehensive Cancer Center and associate director of Translational Research. “I am pleased that our Center was involved in this exciting project and we hope we can be involved in translating this basic research to the clinic.”
Panigrahy said that non-steroidal anti-inflammatory drugs (NSAIDs), which include aspirin and ibuprofen, reduce pain, fever and inflammation “bit may have severe side effects including stomach and brain bleeding as well as severe cardiovascular and kidney toxicity. They also do not specifically enhance clearing of debris.”
“We are exploring all options to translate PTUPB to cancer patients especially in combination with current cancer therapies such as chemotherapy, radiation, immunotherapy, or surgery which either directly or indirectly may generate tumor cell debris,” Panigrahy said. “Our next step is to investigate whether our findings are consistent with clinical studies involving human cancer.”
The Hammock lab has been researching the sEH inhibitor for 50 years. As a graduate student at UC Berkeley, Hammock co-discovered the sEH inhibitor with fellow graduate student Sarjeet Gill, now a distinguished professor at UC Riverside.
"We have a series of papers largely in PNAS, with the Panigrahy group showing first our soluble epoxide hydrolase inhibitors block tumor growth and metastasis when used with omega3 fish oils or with COX inhibitors and the role for these compounds in regulating a number of mediators of cancer growth," Hammock said.
Multiple grants funded the research. Hammock, the 31-year director of the UC Davis Superfund Program, received funds the National Cancer Institute and the National Institute on Environmental Health Sciences. The Panigrahy laboratory is funded by the Credit Union Kids at Heart Team. Other grants came from the C. J. Buckley Pediatric Brain Tumor Fund, Molly's Magic Wand for Pediatric Brain Tumors, the Markoff Foundation Art-in-Giving Foundation, the Kamen Foundation, Jared Branfman Sunflowers for Life, and the Joe Andruzzi Foundation. An NIH T32-training grant funded Gartung's work.
Allison Gartung completed her doctorate at Wayne State University in 2016 and has since served as a postdoctoral research fellow at Harvard Medical School/BIDMC. Highly honored for her work, she won the highest award for a post-doctoral fellow (Santosh Nigam Award) at the 15th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, held in 2017 in Puerta Vallarta, Mexico. She served as a guest editor of a special double-issue of 24 invited world-experts in Cancer and Metastasis Reviews on Bioactive Lipids.
Dipak Panigrahy was accepted into medical school at Boston University at age 17. He trained in surgery with Dr. Roger Jenkins, who performed the first liver transplant in New England. Over the past decade, Panigrahy led angiogenesis and cancer animal modeling in the Judah Folkman laboratory. He joined the Beth Israel Deaconess Medical Center in 2013, and in 2014 was appointed assistant professor of pathology, and currently has a laboratory in the Center for Vascular Biology Research. Panigrahy is the expert on the team for preclinical tumor models and examining novel concepts for cancer therapy at the preclinical stage –the diversity of models he has created and worked with is unmatched.
Bruce Hammock, UC Davis distinguished professor, is the world expert and discoverer of the dual COX2-sEH inhibitor. He received his doctorate in entomology/toxicology from UC Berkeley and joined the UC Davis faculty in 1980. Highly honored by his peers, Hammock is a fellow of the National Academy of Inventors, which honors academic invention and encourages translations of inventions to benefit society. He is a member of the U.S. National Academy of Sciences, and the recipient of scores of awards, including the Bernard B. Brodie Award in Drug Metabolism, sponsored by the America Society for Pharmacology and Experimental Therapeutics; and the first McGiff Memorial Awardee in Lipid Biochemistry,
Mark Kieran of Bristol-Myers Squibb and Professor Vikas Sukhatme (Dean of Emory School of Medicine), both senior co-authors, are leading world-experts on personalized medicine approaches to support the treatment of cancer patients. Kieran is a leading oncologist with expertise in translating novel therapeutic modalities (beyond chemotherapy/irradiation) into the clinic. Plans for clinical trials involving PTUPB are underway.
Professor Sui Huang, with the Institute for Systems Biology (ISB), is known as the world's leading expert on systems biology and debris-induced tumor growth.
Should auld acquaintance be forgot,
and never brought to mind?
No, they won't—at least not for Bruce Hammock, a distinguished professor at the University of California, Davis, and the hundreds of scientists he's trained over an academic career spanning more than four decades at UC Davis and UC Riverside.
Looking back over 2018, Hammock remembers fondly the weekend that 100 of his former laboratory alumni from 10 countries traveled to Davis to honor his work, reunite, collaborate, and reminiscence.
Billed as “Biochemistry and Society: Celebrating the Career of Professor Bruce Hammock,” the three-day event drew Hammock lab alumni from throughout the United States, as well as Egypt, Spain, China, Australia, New Zealand, Germany, Sweden, Canada and the Czech Republic.
“It was really special and I will treasure that weekend always,” said Hammock, who trained scientists at UC Riverside for five years before joining the UC Davis faculty in 1980. He currently holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. He has directed the UC Davis Superfund Program, funded by the National Institutes of Health's National Institute of Environmental Health (NIH/NIEHS), for 31 years.
The distinguished professor, known for his expertise in chemistry, toxicology, biochemistry and entomology, meshes all four sciences in his 50-year research on acute and neuropathic pain in humans and companion animals. It all began with his basic research on how caterpillars become butterflies, research that led to key discoveries about chronic pain.
Since then, his lab has generated more than 80 patents, 300 postdoctoral fellows, and more than 65 graduates, who now hold positions of distinction in academia, industry and government.
Hammock's colleagues, and former postdoctoral fellows, graduate and undergraduate students and visiting scholars arrived at the lab reunion with their spouses--as well as their scientific posters for display and discussion. The posters covered everything from ground-breaking research in prestigious journals to a humorous look at his annual water balloon battles in front of Briggs Hall.
The scientists dined at the UC Davis Conference Center, the Buehler Alumni Center and the Stonegate Country Club; shared months, years and decades of memories; and toasted, roasted and gifted their mentor. Hammock, in turn, toasted, roasted and gifted them.
“We had a blast,” recalled organizer Shirley Gee, a former research toxicologist and manager of the Hammock lab for 31 years. She retired in June 2016 after 40 years of service with the university.
“I have had a vision of this event to honor Bruce for many years now, and it was such a thrill to see it come together,” she said. “Reconnecting in person with all the alumni and their families was more rewarding than I could have imagined, but even more importantly was the thrill of watching alumni reconnect with each other! There were a lot of tears in the house. Many people I think were surprised by how the years melted away when they began reacquainting. I think that speaks to the environment that Bruce created that led to many strong personal and professional bonds.”
Gee credited her seven-member committee—former Hammock students Keith Wing, Jim Ottea, Tom Sparks, Babak Borhan, Qing Li; postdoctoral fellow and “academic grandson” Kin Sing Stephen Lee, a former student of Babak Borhan; and colleague Sarjeet Gill, now a distinguished professor at UC Riverside, with greatly contributing to the success of the one-of-a-kind celebration.
As graduate students, and Hammock and Gill worked together in the John Casida lab at UC Berkeley and later in Larry Gilbert's lab where they co-discovered the enzyme, soluble epoxide hydrolase. Hammock remembers researching juvenile hormones and what's involved in "how caterpillars became butterflies."
Hammock has studied the enzyme system and its inhibitors ever since. He recently formed a Davis-based company, EicOsis, to develop an orally active non-addictive drug for inflammatory and neuropathic pain for human beings and companion animals. Human clinical trials are scheduled to begin in 2019. Several seed-fund grants and a NIH/NINDS (National Institute of Neurological Disorders and Stroke) Blueprint Development Grant support EicOsis.
Hammock, described at the lab reunion as a “genius,” collaborates with scientists worldwide in what's been described as “unprecedented research with a multidisciplinary, integrated approach to research focused on insect biology, mammalian enzymology, and analytical chemistry.” He has authored more than 1000 publications on a wide range of topics in entomology, biochemistry, analytical and environmental chemistry in high quality journals, and has been cited more than 54,000 times. In the epoxide hydrolase field, the Hammock laboratory has published almost 900 peer-reviewed papers.
Tom Sparks, who was Hammock's first graduate student at UC Riverside, chronicled Hammock's career and recalled humorous anecdotes from his early professorship at UC Riverside. A former professor at Louisiana State University, and now a research fellow in Discovery Research at Dow AgroSciences (now Corteva Agriscience, Indianapolis, Sparks praised Hammock's intellect and curiosity. “For Bruce, it was all about the journey, looking around and operative at the interface between entomology, biochemistry and chemistry.”
Gill, along with University of Utah emeritus professor Glenn Prestwich and UC Davis research scientist Karen Wagner also delivered presentations, fondly recalling their shared time and science with Hammock.
Keith Wing, who was Hammock's second graduate student at UC Riverside/Davis, served as emcee at the lab reunion. A former senior research associate at DuPont and Rohm and Haas and current consultant, Wing said “Bruce has inspired many hundreds of developing scientists. For myself and many others, he was able to see what we could become as scientists and social contributors before we could see it ourselves."
Qing Li, a professor in the University of Hawaii's Department of Molecular Biosciences and Bioengineering College of Tropical Agriculture and Human Resources who received his doctorate from UC Davis, studying with major professors Bruce Hammock and James Seiber, said that "Bruce is an eminent scientist and a great mentor. Many of us have benefited from his effective mentorship. Back in 1990, after he signed my dissertation, he shook my hand, and then he asked me to tape-record it and give him the recordings -- a great 'homework' assignment and good practices for me."
Others commented that they learned this from Hammock: “We explore the unexpected and get to do things that don't work” and “Design things to fail; when they don't fail follow along.”
Hammock, the crowd agreed, seems to follow baseball legend Yogi Berra's sage advice: “If you come to a fork in the road, take it.”
Gill praised Hammock's “impact on human health, environmental health” as well as his love of the outdoors—from kayaking to mountain climbing.
Numerous alumni lauded Hammock's sense of humor. One scientist quoted Albert Einstein as saying “Creativity is intelligence having fun” and added “Bruce is always having fun.”
Among the other comments:
- “I never heard him speak a cross word.”
- "He treats everyone with respect.”
- "Bruce loves science and he loves people.”
- "He never heard a crazy idea.”
- "What Bruce does—he delivers the future.”
- "Bruce has a lot of determination and can approach difficult problems from multiple angles.”
- "Bruce values strong relationships with friends he has made over the years”
A native of Little Rock, Ark., Hammock received his bachelor of science degree, magna cum laude, in 1969 from Louisiana State University, Baton Rouge, where he majored in entomology and minored in zoology and chemistry. Then it was off to UC Berkeley, for his doctorate in entomology/toxicology in 1973, and postdoctoral fellowship.
It was at UC Berkeley where he met and married his wife, Lassie, who had just entered the doctoral program in plant physiology. They married in 1972 and then “the Army called me up,” Hammock remembers.
Hammock served as a public health medical officer/first lieutenant with the U.S. Army Academy of Health Science in San Antonio, Texas; and then did more postdoctoral research at the Rockefeller Foundation, Department of Biology, Northwestern University, Evanston. Ill.
Hammock then joined the faculty of the Division of Toxicology and Physiology, UC Riverside Department of Entomology in 1975 before heading for UC Davis in 1980 to accept a joint-faculty appointment in toxicology and entomology.
Bruce and Lassie reared three children: Tom, Bruce and Frances. “Frances and her husband, Adrian, teach math at UC San Diego; Bruce is on the UC Davis School of Veterinary Medicine faculty; and Tom, a graduate of the American Film Institute Conservatory, makes movies,” Hammock said, adding that he and Lassie appeared in one of the movies that Tom directed: "The Last Survivors."
Highly honored by his peers, Hammock is a fellow of the National Academy of Inventors, which honors academic invention and encourages translations of inventions to benefit society. He is a member of the U.S. National Academy of Sciences, a fellow of the Entomological Society of America, and the recipient of scores of awards, including the Bernard B. Brodie Award in Drug Metabolism, sponsored by the America Society for Pharmacology and Experimental Therapeutics; and the first McGiff Memorial Awardee in Lipid Biochemistry.
Hammock told the crowd at the reunion that he began his career studying insect science but switched to human research after encountering “all the suffering involved in acute and neuropathic pain.”
His insect science research centered around how a key enzyme, epoxide hydrolase, degrades a caterpillar's juvenile hormone, leading to metamorphosis from the larval stage to the adult insect. He then wondered "Does the enzyme occur in plants? Does it occur in mammals?" It does, and particularly as a soluble epoxide hydrolase in mammals.
“It is always important to realize that the most significant translational science we do in the university is fundamental science,” said Hammock. “The extreme and poorly treated pain that I observed as a medical officer in a burn clinic in the Army, is a major driver for me to translate this knowledge to help patients with severe pain.”
And it all began with him asking how caterpillars turn into butterflies.
"Science is full of surprises," the distinguished UC Davis professor said. "We need to remember that the concept, the clinical target, and even the chemical structure came from asking how caterpillars turn into butterflies."
“All my life I've known my feet didn't have the strength and capability of most of the people I knew,” she recalled.
In high school, she began experiencing severe pain. Her family physician diagnosed her as having “growing pains.”
It wasn't until after she'd retired from her 34-year career as an elementary school teacher in Concord that a neurologist correctly diagnosed her—and her brother--as having peripheral neuropathy, a disease that afflicts more than 30 million people in the United States alone. Specifically, she and her brother inherited Hereditary Sensory Autonomic Neuropathy or HSAN.
Anderson's journey to learn more about peripheral neuropathy and to help others led her to co-found the Western Neuropathy Association (WNA) in Auburn in 1998, and serve as its president for the last two decades.
Her 20-year journey of hope recently led to the University of California, Davis, where distinguished professor Bruce Hammock is researching an enzyme aimed at controlling acute and neuropathic pain.
Anderson and WNA treasurer Darrell O'Sullivan, a former lab manager at the UC Davis Medical Center, recently visited the Hammock lab to present a $5000 check from the association to EicOsis, the Davis company that Hammock founded to move inhibitors of the soluble epoxide hydrolase into human clinical trials.
“We raised the money through $2,500 from our budget, and from voluntary donations from members and friends,” she said. “One member donated $1000 and asked it to be matched.”
“It was heartwarming to receive a $5000 check from this dedicated, grass-roots group,” said Hammock, whose research on the compounds spans nearly 50 years. “We are touched.”
Anderson and O'Sullivan toured Hammock's lab in Briggs Hall, UC Davis Department of Entomology and Nematology, and discussed his research and the WNA mission and goals.
“There are medications that help the symptoms, but no cure yet,” Anderson said, adding that the Hammock discovery “may be close to a cure for some people who have pain and inflammation.”
"On behalf of EicOsis I want to thank the Western Neuropathy Association, and particularly Bev Anderson and Darryl O'Sullivan, for championing this effort," Hammock said. "Everyone at EicOsis is touched by the confidence they have put in us to develop a treatment for chronic pain. There are never guarantees in drug development, but certainly their support drives us to work hard to move this drug through FDA and on to clinical trials."
"We are, of course, working to raise support from federal agencies, venture funds and the pharmaceutical industry, but this support from Bev and her associates is heartfelt and inspiring. It illustrates what a great need there is to develop treatments for pain," Hammock said. "The fact that the support is coming from so many of the people who are suffering from pain is particularly inspiring."
"It is inspiring about how upbeat the individuals are in these organizations as they support each other and exchange approaches in dealing with pain," he pointed out. "But underlying these optimistic conversations is the reality that pain can be an overpowering factor compromising the leading a full and health life. We must find a solution to the problems of pain and neuropathy."
The clinical trials, expected to begin next year, will target chronic or neuropathic pain with a non-opiate analgesic. In parallel, Hammock and his UC Davis colleagues are developing a drug to treat a commonly fatal pain condition in horses called laminitis as well as arthritic pain in dogs and cats.
Hammock traces the history of his work to 1969 to his graduate student days in the laboratory of UC Berkeley Professor John Casida. Hammock was researching insect developmental biology and green insecticides when he and colleague Sarjeet Gill, now a distinguished professor at UC Riverside, discovered the target enzyme in mammals that regulates epoxy fatty acids.
“The work led to the discovery that many regulatory molecules are controlled as much by degradation and biosynthesis,” Hammock said. “The epoxy fatty acids control blood pressure, fibrosis, immunity, tissue growth, pain and inflammation to name a few processes.”
Peripheral neuropathy is a complex disease. It refers to “the many conditions that involve damage to the peripheral nervous system, the vast communication network that sends signals between the central nervous system (the brain and spinal cord) and all other parts of the body,” according to the National Institute of Neurological Disorders and Stroke. “Best known are the signals to the muscles that tell them to contract, which is how we move, but there are different types of signals that help control everything from our heart and blood vessels, digestion, urination, sexual function, to our bones and immune system. The peripheral nerves are like the cables that connect the different parts of a computer or connect the Internet. When they malfunction, complex functions can grind to a halt.”
“There are over 150, some say over 200, known causes of neuropathy,” said Anderson, a resident of Colfax. “Diabetes is considered a chief cause. but chemotherapy and likely hereditary neuropathies are gaining on it.”
Although the peripheral neuropathy she has is HSAN, “there are10 or more hereditary types,” she said. “HSAN is unique in its early onset as I could have been diagnosed by kindergarten if medical science had been up to it then.” The neurologist who correctly diagnosed her told her she had “The neuropathy walk.”
“One aspect is that toes naturally go outward for better balance,” Anderson explained. “I call them my ‘outrigger toes.' With neuropathy, it usually starts with tingling like the foot is asleep and waking up and progresses into numbness. Pain of various types and intensities may follow. It boggles the mind to have feet so numb that surgery could be done on them without anesthesia but they still have pain. It depends on the amount of nerve damage.”
“There is a long list of other symptoms: sensory ones like feelings of hot or cold when the feet or hands are not hot or cold to the touch, deep itching, feeling like you are wearing a stocking or glove when you aren't, etc., motor ones like balance, and movement concerns, and autonomic ones that are internal as all internal organs are operated by peripheral nervous system. Blood pressure, kidney function, urinary tract, digestive system, sexual feelings, etc. are affected by the health of the nerves.”
Anderson noted that neuropathy “usually starts in the longest nerve which is the one that goes to the toes. When the progress gets up to the knees, it may start in the fingers and hands as that is now about the same length. However, it may also start in the hands if the injury that causes the neuropathy is in the cervical spine area initially. “
The mission of WNA, comprised of 500 members and many other attendees in California, Oregon and Nevada, is “to provide support, information and referral to people with neuropathy and to those who care about them, to inform and connect with the health care community and to support research,” Anderson said. The all-volunteer organization seeks to establish and develop support groups in as many cities as possible.
Highly honored for his work, Hammock is a member of the National Academy of Sciences and the National Academy of Inventors. He received an outstanding achievement award from the international Eicosanoid Research Foundation at its 2017 meeting in Puerto Vallarta, Mexico, where he delivered a plenary lecture on “Control of Acute and Neuropathic Pain by Inhibiting the Hydrolysis of Epoxy Fatty Acid Chemical Mediators: Path to the Clinic.”
Hammock's career took him from UC Berkeley to the U.S. Army Academy of Health Science in San Antonio, Texas; to a Rockefeller Foundation Fellowship at Northwestern University, Evanston, Ill., and to UC Riverside, where he served as an assistant and associate professor before he joined the UC Davis faculty in 1980. He holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Center for Cancer Research.
Hammock collaborates with scientists worldwide in unprecedented research with a multidisciplinary, integrated approach to research focused on insect biology, mammalian enzymology, and analytical chemistry. He has authored more than 1000 publications on a wide range of topics in entomology, biochemistry, analytical and environmental chemistry in high quality journals. In the epoxide hydrolase field, the Hammock laboratory has published almost 900 peer-reviewed papers.
“For many years Sarjeet and I were alone in studying this enzyme and pathway but now its importance is well recognized in mammalian biology with over 17,000 peer reviewed papers in the area,” Hammock said. “The importance of this pathway is now clear.”
The Hammock laboratory is the home of the UC Davis/National Institute of Environmental Health Sciences Superfund Program. The laboratory has generated more than 80 patents, 300 postdoctoral fellows, and more than 65 graduates, who now hold positions of distinction in academia, industry and government.
“It is always important to realize that the most significant translational science we do in the university is fundamental science,” said Hammock. “The extreme and poorly treated pain that I observed as a medical officer in a burn clinic in the Army, is a major driver for me to translate this knowledge to help patients with severe pain. Hopefully, we can start human clinical trials next year.”
Bev Anderson and fellow members of WNA hope so, too. It's been a long journey, from misdiagnosis to rays of hope to bursts of optimism.
Casida, 88, one of the world's leading authority on how pesticides work and their effect on humans, died June 30 of a heart attack in his sleep at his home in Berkeley. He was considered the most preeminent pesticide toxicologist over at least the last two centuries.
A distinguished professor emeritus of environmental science, policy and management and of nutritional sciences and toxicology, Casida was the founding director of the campus's Environmental Chemistry and Toxicology Laboratory.
When awarded the Wolf Prize in Agriculture in 1993, the Wolf Foundation lauded his “research on the mode of action of insecticides as a basis for the evaluation of the risks and benefits of pesticides and toxicants, essential to the development of safer, more effective pesticides for agricultural use." according to a UC Berkeley News Service story. "His discoveries span much of the history of organic pesticides and account for several of the fundamental breakthroughs in the fields of entomology, neurobiology, toxicology and biochemistry.”
Former graduate student Bruce Hammock, now a distinguished professor at the University of California, Davis, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, remembers him as a “lifelong mentor who evolved into a colleague and a friend.”
“John continued his high productivity until his death with major reviews on pesticides in 2016, 2017, and 2018 in addition to numerous primary papers,” Hammock noted. “He was working on primary publications as well as revising his toxicology course for the fall semester at the time of his death. Pesticide science was the theme of his career, and we live in a world with far safer and more effective pest control agents because of his effort.”
John Casida opened multiple new fields ranging from fundamental cell biology through pharmaceutical discovery. "He pioneered new technologies throughout his career, from being one of the first to use radioactive compounds for pesticide metabolism through studies with accelerator mass spectrometry, photoaffinity labeling and others," Hammock related. "Yet the greatest impact of his career probably lives on in the numerous scientists he trained, now carrying on his traditions of excellence in science. These scientists are around the world in governmental, industrial and academic careers.”
As compiled and shared by Hammock, below are comments from a few of his doctoral students and postdoctoral fellows who worked both with Casida at UC Berkeley and at, least for a time, also were at UC Davis.
Distinguished Professor of Cell Biology and Neuroscience, University of California, Riverside
"This project also allowed me to build a long lasting friendship with Bruce Hammock who also was on the same project. Since John was always very focused, I often challenged John's patience with my practical jokes. I am sure he knew who the culprit(s) were but he never revealed he knew.
“The research experiences in John's lab made an indelible impression on me that drove me to return to the United States from Malaysia for an academic career in the UC system. Personally, I have lost an incredible mentor, and the scientific community lost the most preeminent pesticide toxicologist in the last two centuries. John changed the way we investigated mechanisms of toxicity at all levels. I certainly will miss him dearly.
Distinguished Professor at the University of California, Davis: Joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center
"After telling him I was there to be his graduate student, he replied he had no money for students. My retort was that I had a fellowship. He then told me that students were not space effective, and I promised not to take up much space. He continued that students were not time effective, and I promised not to take his time. In retrospect, Sarjeet must have really soured him on graduate students a few hours earlier."
"Months later, Sarjeet and I were sharing a desk-lab bench in the windowless closet next to the 'fly room' when Dr. Casida walked in. He had noted we both listed him as our major professor and asked if there was anything, he could do to encourage us to leave. When in unison we replied 'No!,' he politely left without accepting us, but soon we both had a desk and bench.
"So a few paces after Sarjeet, I initiated the most thrilling four years of my life. John's introduction to experimental science was marvelous with the perfect balance of inspiration, instruction and tremendous freedom. I was privileged to learn from a wonderful group of individuals and, of course, I made my most enduring of friendships with Sarjeet Gill. In addition to science, John taught a life-family-science balance by example. John was my life long mentor in science and in life but also evolved as a colleague and friend.
"Three more delightful years passed and John then took me to lunch at the faculty club. As I was about to leave the laboratory for the U.S. Army, he gave me sagely advice such as he had had it easy during the Sputnik period and I would have it hard. Then he went on to tell me than most people in the laboratory did not find my practical jokes nearly as funny as I did. I did not reveal that Sarjeet had both planned and executed most of them. Thus, Sarjeet succeeded in disrupting my Berkeley career from beginning until the end.
"John and his laboratory at Berkeley provided me with the most exciting years of my scientific career. In his own work, John moved from strength to strength creating numerous entire fields along the way. His scientific insight and drive were a constant stimulation to drive for innovation and excellence. Whenever I had an opportunity, I encouraged others to join his team. John was an inspiration and role model, not only because John came in early and stayed late, but also because he did science for the fun of discovery and taught for the joy of teaching."
Keith Wing Consulting LLC
Life Science Industrial Biochemistry or Biotechnology
"While we all worked hard including many evenings and weekends, there were times when I or other American rebels would lead a mass lab exodus for a salmon fishing or ski trip during (gasp!) regular business hours. John would pretend to barely notice our ill-disguised escape along the cabinets that lined the Wellman Hall basement, except to raise his right eye from his manuscript editing in an unmistakable sign of disapproval at our lack of scientific drive.
"And this leads to another Casida work pattern of the time…. All of us scientists were subject to John's multiple cycles of manuscript editing. We would wrack our brains trying to put the right words and figures down as manuscript drafts, submit them to John, and wait for three days or less for him to return it to us in a sea of thin red ink, and the humbling realization that we really were much poorer writers than we'd thought. After discussion with John and acquiescing to practically every edit he'd made, the manuscript would be re-typed manually by his administrative assistants in entirety and the cycle would repeat but with less red ink. After at least three cycles of this, we'd submit the manuscript for publication, often with a high acceptance rate. With time, we all came to understand and see John's wisdom in approaching publication and science contribution. All of this occurred right as word processing programs had started taking hold in the outside world, and perhaps my one service to the lab on my 1983 exit was to convince John to look into using word processing/saving documents on disks for editing. Oh, and maybe a bit of science as well.
"John Casida's lab has been the world leader in examining both pesticide metabolism and their biochemical target sites. I was lucky enough to work on a project that combined both, and it molded the way I looked at insecticide discovery in industry. The interdisciplinary approach to the mechanisms by which xenobiotics interface with biological systems influenced the thinking of every person who has passed through John's lab. That influence has proliferated throughout the world and has advanced the field of pesticide toxicology to what it is today. We mourn the loss of a great leader but understand that his alumni are a large international family that will carry his spirit and teachings forward."
Andrew 'Andy' Waterhouse
Director of the Robert Mondavi Institute for Wine and Food Science and Professor of Viticulture and Enology,
University of California, Davis
"A couple of weeks after I arrived, he showed me Don Crosby's book on natural toxicants, and asked if I would confirm the very high toxicity of ryanodine mentioned therein. The high toxicity suggested strong binding to a key regulatory protein, and its novel and unknown mode of action made it an exciting prospective target. Confirming that ryanodine was in fact a deadly toxic, he set a project in motion to discover the site of action, hiring Isaac Pessah to use the yet-to-be-made radioligand on a hypothetical site of action!
"We were astonishingly lucky to find that the natural source of ryanodine contained a major impurity that was one step away from the highly radioactive form, so it wasn't too long before we had very hot ryanodine available. Initial attempts detected no binding at all, but Isaac thought to add some calcium to the assay, and we had the binding site in hand! This discovery essentially established a field of science in muscle physiology and pharmacology, with entire symposia dedicated to exploring this binding site and its broader significance to toxic modes of action. Isaac is an established leader in the field. It was a real privilege to see how groundbreaking research can happen and be part of it, and to get to know all the fabulous scientists that John collected around him."
Associate Dean of Research and Graduate Education, and Professor, Department of Molecular Biosciences, UC Davis School of Veterinary Medicine
University of California, Davis
"I remember most vividly my reaction when John also indicated that working on the biochemistry GABA receptors, my original intent for traveling across country for a postdoc, was not to be. ‘Work on something else' John advised, ‘there are so many interesting unanswered questions around the PCTL.' Arguably John's straightforward and highly insightful advice changed the course of my professional life. He introduced me to chemist Andy Waterhouse, and the next two years of work that led to the discovery and identity of the ryanodine receptor were breathtaking. Our discovery benefited from many factors; a gift from Ryania speciosa in the form of didehydroryanodine, which Andy identified, the newly published use of palladium catalyst to catalyze efficient reduction of minute quantities of unsaturated bonds, the National Tritium Laboratory just above the PCTL…and of course, there was John's unwavering support for discovery, no matter how risky. Successful synthesis of [3H]ryanodine and identity of its receptor paved the way to immense basic discoveries in virtually every field of science, identification of several disease causing mutations of skeletal and cardiac muscle and the nervous system, and successful discovery of highly selective ryanoid insecticides. Since the first paper published in 1985, there have been nearly 20,000 peer reviewed publications (ISI Web of Science) and a search on Google Scholar yields more than 70,000 hits. To many, John was the recognized leader in pesticide chemistry and toxicology. I agree, although from my perspective, John was also a true renaissance individual, seeding ideas of great significance in so many fields, of which ryanodine receptors represents only one of many. His love of science and discovery positively impacted his students and postdocs. He will be fondly remembered and sorely missed.'
Professor, Department of Molecular Biosciences and Bioengineering College of Tropical Agriculture and Human Resources, University of Hawai‘i at Mānoa
" In April 2018, I had a couple of telephone conversations with Professor Casida. He shared with me what he was doing (of course, writing manuscripts), his health, Kati's health, his sons and his grandkids. We talked about meeting at the Biochemistry and Society: Celebrating the Career of Professor Bruce Hammock, to be held in Davis in August 2018. We talked about a possibility to attend a meeting together in China in 2019.
"I was privileged to manage Professor Casida's manuscript entitled 'Pesticide Detox by Design' that he submitted to the Journal of Agricultural and Food Chemistry. This is Professor Casida's last manuscript, I believe. It is still in the review process. He wrote that 'Detoxification (detox) plays a major role in pesticide action and resistance…' A reviewer who reviewed the manuscript wrote me “I just heard that Professor Casida has passed away... Professor Casida was a giant in pesticide science, a special and unique person. It is a great loss to the pesticide science community…”
Professor Casida is survived by his wife, artist and sculptor Kati Casida, sons Mark and Eric Casida, and two grandchildren.
- John Casida Obituary, UC Berkeley News Service
- For the Fun of Science: A Discussion with John E. Casida (Archives of Insect Biochemistry and Physiology)
- Still Curious: An Overview of John Casida's Contributions to Agrochemical Research (JAFC)
- Curious about Pesticide Action, by John E. Casida (JAFC)