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)
The grant, “Food Quality in Egypt: Screening for Contamination with Pesticides using Innovative VHH Antibody-Based Assays and Biosensors,” was one of 15 collaborative projects selected for funding by the U.S.-Egypt Science and Technology Joint Board. The grants foster research collaboration between Egyptian and U.S. scientists.
“Zagazig is one of the world's premier agricultural institutions,” said Hammock, a distinguished professor who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “I am thrilled to have this support to expand our long collaboration with Zagazig. This is very practical work with potentially profound outcomes on reducing exposure of consumers and workers to pesticides. We are using a very sophisticated new antibody technology to allow on site monitoring of potentially dangerous pesticides.”
“Our postdoctoral scientist Natalia Vasylieva is the star on the project,” Hammock said, “but it encompasses our entire immunoassay group. We have a long-term collaboration with Zagazig University.”
The grants are funded by the National Academies of Sciences, and the Egyptian Science and Technology Development Fund. Reviewers evaluated the proposals' scientific and technical merit, relevance to program objectives, capabilities of partner institutions and individuals, nature of collaboration, and cost-effectiveness. The board funded less than 12 percent of the eligible proposals.
“Immunoassay (ELISA) is an alternative and complimentary analytical method to instrumental techniques like liquid or gas chromatography,” said Vasylieva, who leads the immunoassay group in the Hammock lab. A native of the Ukraine, she received her master's degree from Taras Shevchenko National University of Kyiv, Ukraine, and her doctorate from National Institute of Applied Sciences in France. Joining the Hammock lab in May 2013, she focuses her research on development of nanobodies as neutralizing agents for small molecule poisoning, as well as use of nanobodies as therapeutics.
“ELISA is also considered cheaper method,” said Vasylieva. “Particularly, ELISA is economically interesting when relatively large set of samples have to be analyzed. This is usually the case in the environmental monitoring for contamination and human exposure studies.”
The Hammock lab, which has extensive experience in development of immunoassays, extends the field by developing new formats of the immunoassays by developing new reagents. “In particular, we develop new type of antibodies, called nanobodies or VHH (from variable heavy domain from heavy chain only antibodies) that naturally occur in camelids and sharks,” Vasylieva said. “These antibodies have all the affinity properties of conventional (polyclonal and monoclonal) antibodies, but also have unique properties, like small size (1/10th of the size of conventional antibodies), high thermal stability, resilience to organic solvents and high refolding capacity. These properties make them particularly suitable for use in portable devices for environmental and human exposure monitoring.”
A large amount of pesticide is used in Egypt,” she said. “So far, only limited amount of information is available about environmental contamination and human exposure to those pesticides. In these few publications available, levels of pesticide in the food appears to be over the allowed limits.”
In their abstract, the researchers explained that long-term application of pesticides has resulted in contamination of food in Egypt. “Continuous exposure to pesticides is usually associated with infertility, birth defects, endocrine disruption, neurological disorders and cancer in humans. Worldwide reliance on chemical pesticides in agriculture remains an essential component for high food production. According to the Egyptian Agricultural Pesticide Committee, the amount of pesticides imported and used for agricultural production has more than doubled from 2005 to 2012. However, only a few studies have been published on this subject over the past 10 years and they show high levels of pesticides in a variety of food products.”
“Food monitoring studies in Egypt have been primarily limited to analysis of organochlorides, organophosphates, and carbamate insecticides,” the researchers noted in their abstract. “Research and monitoring of other pesticide groups is a relatively new subject, and a knowledge gap still remains. With this study, we propose to assess the safety of food available on the Egyptian market and develop tools for fast and low-cost contamination screening. Our long-term goal is to contribute to a healthier Egypt by raising awareness about food chemical safety and to provide simple tools for researchers and stakeholders to screen the food products for compliance with regulatory policies. We hypothesize that human exposure to toxic chemicals through contaminated food (domestic and imported) has increased due to excessive application of pesticides in order to face nutrition needs.”
They defined three specific goals of the project:
- To screen Egyptian domestic and imported food samples for pyrethroid insecticide residues, a major group of insecticides used today, using immunoassays;
- To develop new reagents and immunoassays for detecting diamide insecticides, a group of pesticides whose use is rapidly growing, and
- To develop tools for fast and low-cost food contamination screening in the environment with minimal technical support.
Overall, the scientists aim to develop innovative immunoassays and biosensors empowering scientists and engaged Egyptian communities to collect analytical data to address environmental chemical concerns. “We will do this by adapting and refining technologies to improve assay performance, reliability and field portability,” they wrote. “The knowledge gained from this research will provide insight into human exposure to agricultural pesticides in Egypt and will raise the Egyptian population's awareness of food quality.”
Hammock, a member of the National Academy of Sciences and the National Academy of Inventors, directs two major UC Davis programs; the Superfund Program financed by the National Institute of Environmental Health's National Institute of Environmental Health Sciences (NIH-NIEHS); and the NIH Biotechnology Training Program. Hammock, who holds a doctorate in entomology/toxicology from UC Berkeley, served as a public health medical officer at the U.S. Army Academy of Health Science in San Antonio, Texas; a postdoctorate fellow in entomology/toxicology at UC Berkeley; and a postdoctoral fellow in biochemistry with the Rockefeller Foundation, Northwestern University, Evanston, Ill., before joining the UC Davis faculty in 1980.
Xu, professor of agro-ecology at the China Agricultural University (CAU), is on a yearlong sabbatical in the Hammock lab. He received assistance in obtaining the grant from project manager Bruce Hammock and program manager Shirley Gee, now retired, both co-investigators.
“This is a highly competitive program and this grant is a huge honor for Ting and for Shirley Gee,” said Hammock, who holds joint appointments in the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Center.
The $330,000 grant, funded by China, is a cooperative agreement between UC Davis and China. “The grant is quite timely, as UC Davis is working to increase scientific exchange with China,” Hammock said. “We have been collaborating with Ting's group for several years on nanobody-based immunoassays to improve human and environmental health.”
Two previous students from Professor Xu's laboratory have studied in Davis and the funds will allow additional senior Ph.D. students from Xu's laboratory to join the Hammock lab.
Xu described immunoassays as “a rapid, sensitive and cost effective method of analysis for pesticides.” Technically, engineering antibodies “such as a variable domain of heavy chain antibody (VHH) from camelids and a single-chain antibody variable fragment (scFv) from chickens have advantages over monoclonal and polyclonal antibodies in the respect of small size, thermal stability, solubility and easy generation,” Xu explained. “The objectives of this project focus on the production of specific VHHs and scFvs for several pesticides and the development of engineering antibodies based immunoassays for pesticide environmental exposure and food safety. The novel pesticide antibodies are expected to improve the assay sensitivity and stability.”
“Nanobodies are revolutionizing immunoassay development and possibly disease therapy,” explained Shirley Gee, UC Davis collaborator on the proposal. “It was thrilling over the last few months to have Ting and his student here at the same time as Gualberto Gonzalez from Uruguay and his students since we are three of the major labs developing this technology for analyzing environmental and food toxins.”
Among other benefits, the research can aid farm workers, who would be monitored for pesticides in their urine. The assay could distinguish between exposed and unexposed populations and provide useful information about relative exposure related to crop or use of personal protective equipment.
Xu's publications directly address the fact that the immunoassay method, especially ELISA, is an effective screen tool for the agrochemicals and pollutants in the environment. His main contributions to science are associated with design of novel haptens, production of tradition (monoclonal and polyclonal) and engineering antibodies, and development of competitive and non-competitive enzyme-linked immunosorbent assays (ELISA) for small molecules.
Xu received his doctorate in agro-ecology in 2003 from CAU, and did postdoctoral research in immunoassays in 2007 at the University of Hawaii. He joined the CAU faculty in 2003 as a lecturer and advanced to associate professor in 2007, and professor in 2013. Twice honored by Chinese governments, Xu received third prize for the Agriculture Science and Technology Award by the China Ministry of Agriculture in 2009, and second prize for the Technological Invention Award by the China Ministry of Education in 2013.