John Edward Casida (1929–2018)

John Edward Casida (1929–2018)

An honorary member of the Pesticide Science Society of Japan, Dr. John Edward Casida passed away on June 30, 2018 in California. In the name of the Pesticide Science Society of Japan members, Japanese alumni of Casida laboratory, friends and acquaintances, I offer my heartfelt condolences to Casida family.

Dr. Casida contributed immensely to the establishment of the Pesticide Science Society of Japan. It was he who named it as “Pesticide Science Society of Japan (PSSJ)”. When the Society was first established in 1975, he gave the memorial speech entitled: “US–Japan Cooperative Pesticide Research:16 Year Progress Report from one Laboratory.” Prior to this event, in accordance with the scientific exchange project by the Japan Soc. for the Promotion of Science (JSPS)–US National Science Foundation (NSF), together with Dr. Kazuo Fukunaga (later the first President of the PSSJ), Casida organized the first pesticide related symposium (1967)—Pesticide metabolism, degradation and mode of action. This so-called “Nikko symposium” has had an immense impact on the development of pesticide science and technology in Japan.

Dr. Casida was born on December 22, 1929 in Phoenix, Arizona. Later the family moved to Wisconsin, where his father became professor at the University of Wisconsin, where John became professor as well. In those days, DDT and parathion were still in the heyday of their popularity. Yet, warning issued by Raechel Carson’s “Silent Spring” has begun to cast doubt on pesticide safety to man and environment. With this background, research of mode of action of insecticides with a view to safer environmental impact done by Casida contributed greatly to toxicological, physiological and biochemical understanding. The University of Wisconsin, Madison (1954–63) and Casida Laboratory of Environmental Chemistry and Toxicology at the University of California, Berkeley (1964–2018) became a meeting point for many scientists, both domestically and internationally. His research paper and books have numbered up to 850 and patents up to 30 over the 50 years period, which have had great impact on the field of insecticide chemistry and toxicology. Alumni of Casida Laboratory are over 230, including about 30 Japanese scientists (Table 1).

Table 1. List of the Japanese alumni

Name	Period at Casida’s Lab.	Affiliationc)
Tadao Watanabea)	1963b)	Kyushu Univ.
Morifusa Etoa)	1959–60; 1973–74	Kyushu Univ.
Yoshihiko Nishizawaa)	1965b)	Sumitomo Chemical
Shozo Kuwatsukaa)	1965b)	Kyushu Univ.
Izuru Yamamoto	1964–67 ; 1970–71	Tokyo Univ. of Agric.
Masuhisa Tsukamoto	1964–66	Osaka Univ.
Jun-ichi Fukami	1964–66	Riken (Inst. Physic. & Chem.Res.)
Hisayuki Matsuo	1970b)	Riken
Hideo Kamimura	1968–71	Nihon Soda
Hideo Ohkawa	1969–71	Kyushu Univ.
Kenzo Ueda	1971–74	Sumitomo Chemical
Tomihiko Ohsawa	1972–74	Riken
Tadaaki Unai	1974–77	ex−Tokyo Univ. of Agric.
Toshio Shono	1975–78	Tsukuba Univ.
Masayoshi Eto	1977–79	Himeji Women’s College
Kanju Ohsawa	1977–79	ex−Tokyo Univ. of Agric.
Matazaemon Uchida	1979	Nihon Noyaku
Shinkichi Tawata	1979–82	Kyushu Univ.
Takashi Suzukia)	1981b)	Tohoku Univ.
Tetsu Ando	1980–82; 1988–90	Tokyo Univ. of Agric. & Tech,
Akinori Hirashima	1983–85	ex−Kyushu Univ.
Osamu Kirinoa)	1985b)	Sumitomo Chemical
Masafumi Matsuzawa	1984–86	KI Institute
Norihiro Kawamura	1986–88	KI Institute
Mitsuhiro Ichinari	1990–92	Shionogi
Minoru Yoshida	1992–94	Inst. Env. Toxicology
Motohiro Tomizawa	1993–2009	ex−Tokyo Univ. of Agric.
Yoshihisa Tsukamoto	1997–99	Sankyo
Shinzo Kagabu	1999	Gifu Univ.
Michihiro Kamijima	1997–99	Nagoya Univ.
Hideo Honda	2004–06	Mitsui Chem.Agro.

^a) Passed away ^b) The year of the first paper ^c) Affiliation when they joined Casida’s Lab.

Among those who had studied under Dr. Casida, many have taken up leading roles in academic and industrial fields worldwide. Among Japanese, 18 have become university professors. Four have served as President of PSSJ, which are, Eto (Morifusa), Shono, Ohkawa and I. Those awarded by PSSJ were: Eto (Morifusa), Kuwatsuka, Ohkawa, Unai, Shono, Ohsawa (Kanju), Uchida, Ando, Hirashima, Kirino, Ichinari, Tomizawa, Tsukamoto (Yoshihisa), Kagabu and I. Furthermore, Fukami, Eto (Morifusa), Kuwatsuka, Shono, Ando and I were awarded Japan Prize of Agricultural Science/The Yomiuri Prize of Agricultural Science.

There are also awardees from the alumni of the International Award for Research in Pesticide Chemistry: Eto (Morifusa), Ohkawa, Kagabu and I. These awards are not only the honor for each of them, but they illustrate the major impact that Dr. Casida has had on our field.

Considering all the works of Dr. Casida, PSSJ conferred a distinguished service award on Dr. Casida (1995). He also became an honorary member of the Society in 2005.

Reading through the scientific reports (1951–2014) by Casida, as well as from my personal contact with him during my days in his laboratory, I have appreciated the depth of his knowledge in the fields of organic chemistry, biochemistry, toxicology, environmental and pesticide problems. He had acute sense for distinguishing the main issues of a problem. Casida took a leadership role in the field and gathered talented people from all over the US and abroad for elucidation regarding such issues. The more precise overview of his accomplishment shall be done by someone else. Here I shall go over the involvement of the Japanese scientists in this matter. See Table 2.

Table 2. The Japanese contributors to the Casida’s achievements

Project	Names of contributors
Organophosphorus	Eto (Morifusa), Tawata, Eto (Masayoshi), Hirashima, Kirino, Yamamoto, Ozoea), Fujitaa), Tomizawa, Yoshida, Kamijima, Oshimaa)
Carbamates	Tsukamoto (Masuhisa), Eto (Masayoshi)
Pyrethroids	Nishizawa, Yamamoto, Ueda, Unai, Shono, Ohsawa (Kanju), Ando, Krino
Synertgists	Kuwatsuka, Ohkawa
Rotenoids	Nishizawa, Fukami, Yamamoto, Unai, Fukunagaa), Shishidoa)
GABA-related	Kamijima, Tomizawa
Neonicotinoids, nicotinoids	Yamamoto, Kagabu, Tomizawa, Honda
Others, interacting with nicotinic receptor	Tomizawa, Kagabu
Herbicides	Ohkawa, Suzuki, Kirino, Matsuzawa
Others
Insect ecomones	Watanabe, Kuwanoa)
Juvenile hormone mimics	Yamamoto, Kamimura
Insect growth regulator	Uchida
GSH S-transferase	Ohkawa, Yamamoto
Nucleic acids	Nishizawa
Dinitrophenolic compounds	Matsuo
Polycyclic compounds	Yamamoto, Ohsawa (Tomihiko), Eto (Morifusa), Kawamura, Matsuzawa
Dioxins	Yamamoto
Nikkomycin	Ando
Convulsants	Kawamura
Avermectin	Tsukamoto (Yoshihisa)
[3H]EPTC prep	Ichinari

^a) Not the alumni.

Of the Casida’s achievements, most are interrelated, as exemplified by the following: Nishizawa synthesized [¹⁴C]labeled rotenone and [¹⁴C]labeled chrysanthemic acid, from which I prepared several pyrethroids. Concurrently, Tsukamoto developed stable in vitro metabolic system for the study of carbamate metabolism in insects. Immediately I used this system for the study of insect metabolism of pyrethroids; Fukami and I then studied rotenone metabolism. This system was used by Kuwatuka for the metabolism of methylenedioxiphenyl synergists as well. The obtained findings had far reaching consequence to mammalian metabolism, photodegradation pathway, mode of action of synergists to pyrethroids.

Unai and I tried to prepare demethylated rotenone, one of the photodegradation products, when the reverse of one asymmetric carbon at the side chain occurred. By remethylation, both rotenone and rotenone steric isomer were obtained. Through this reaction, many rotenoid isomers were obtained and structure–activity relationships of rotenoids were obtained. [¹⁴C]labeled rotenone and its isomers were prepared by using [¹⁴C]labeled methylating agent, much easier than using the Nishizawa method. This labeled rotenone was used as radioligand for the detailed study of electron transfer system.

Fascinatingly, Casida group developed many radioligands to investigate insecticide and drug interaction with neurotransmitter-receptors: for instance, GABA-related Cl channel blocker [³H]EBOB or nicotinic acetylcholine receptor ligands [³H]imidacloprid and [³H]acetamiprid. Furthermore, Casida group identified target subunits for the mitochondorial complex I inhibitor using the [3H]trifluoromethyldiazirinyl-pyridaben. More importantly, azidoneonicotinoids, azidonicotinoid and azidoepibatidine (both [1H] and [3H] forms) successfully led to define the interaction of nicotinic ligand at the target surface, thereby contributing to design nicotinic compounds with a novel pharmacophore(s).

Those days when Japanese academics first started to study in the US were times of the cold war between US and USSR, both countries vying with one another in science and technology. In the Casida laboratory, atmosphere was such that, visiting academics were able to display their full ability under his leadership. This atmosphere of comradeship and freedom was because he showed himself to be a top-rated scientist with warm human feelings. For Casida, science offered him a constant joy of discovery. This “joy” has spread beyond him through research and academic institutes, resulting in various great accomplishments.

Personal exchanges with Casida continued even after the academics left his laboratory. Some repeatedly returned to his laboratory. For personal touch, Mrs. Kati Casida, who is an accomplished artist, has created her own brand of Christmas cards, which were sent to friends. Alumni books which were issued occasionally also contributed much to the personal ties among friends. Casida had expressed his wish just before his passing away, that is, he would continue for another two years in education and then, finally retire. This was his retirement plan with his wife, which failed to materialize to our great sorrow.

When a great man dies, people say “A great star fell.” But I would say, “Super nova exploded.” As a star, light emanated from him has gone through the academic world and among researchers. When its life ends, various elements by explosion are scattered throughout the universe, in turn, creating numerous stars. As a super nova, although Casida has passed away, his work will be carried to the far end of the universe, and to futures to come. In thought of him that spans from past to present and to future, I express my deep sorrow on one hand and admiration on the other hand over Dr. Casida.

• Honors selected

Personal recollection

Starting with Morifusa Eto, whose achievement at Casida laboratory had won the good name for Japanese scientists, more and more scientists from Japan came into Casida laboratory. I was one of them and was given a task of micro synthesis of radio-labeled pyrethroid insecticides, which was the untrodden field for me then. Study of metabolism in insects was followed and starting with this, a substantial study on pyrethroids took place at Casida laboratory. Having taken on this study with some achievement, my status as a foreign researcher was upgraded and I was granted participation in the training course for the pesticide researchers at North Carolina State University which lasted several weeks. Day after day, prominent researchers like Casida gave lectures. I happened to be the only Japanese at the workshop. Then and there, I made the acquaintance with such scientists as R. D. O’Brien, E. Y. Spencer, R. L. Metcalf, T. R. Fukuto and A. S. Perry. Never did I foresee then that, years later, my daughter Rica would marry Perry. After the two and a half years’ study abroad from 1964, I returned to Japan in 1967.

In 1969, as a part of US–Japan pesticide cooperation by JSPS-NSF, Biochemical Toxicology of Insecticides symposium was held: O’Brien and I as US and Japan organizers, respectively. One day, out of the blue, Casida contacted me: he wanted to know if I would be willing to take on his laboratory during the period of his sabbatical leave. Those days Japanese universities were in the heat of students’ movements, dealing with extremist factions and university reforms. Moreover, I had just come back to Japan. Still, what seemed impossible was made possible by generosity and understanding on the part of Rector of Tokyo University of Agriculture-T. Naito and I was granted to join UC Berkeley again, also in the heat of students’ movement of anti-Vietnam war. A year and a half stay began in 1970 at Casida laboratory. As his stand-in, I was involved in directing research, negotiations, participation in on-, off- campus committees, and conferences. During this period, I was fully engrossed in widening the field of research for enlightenment.

At that time Entomology Department of UC Berkeley was also the world center of biological control of pest insects and integrated pest management. I shared lectures for the graduate students with the great authority on biological control, R. van den Bosch on Positive and Negative Impact of Chemical and Biological Controls. Through him I was able to deepen my understanding on the implementation of as well as pest control in general. This led me to my taking part in biological and chemical controls of boll weevils at Texas A & M University in 1975.

As I follow the track of my career, it is no exaggeration to say that Casida was the turning point of my life.