MARCH 2007 VOLUME 20, NUMBER 3 © Copyright 2007 by the American Chemical Society
In Memoriam: Christopher J. Michejda (December 19, 1937-January 9, 2007) With the tragic and premature death of Christopher J. (Chris) Michejda earlier this year, our community has lost a most influential champion of the view that chemistry is an essential, coequal discipline among all those that contribute to progress in biomedical research. Chris proved that many times over with his own laboratory program and, equally importantly, with his leadership and organizational activities designed to bring investigators with differing backgrounds together to create fertile opportunities for collaborative interdisciplinary interaction.
prominent Polish family in Silesia during the tense period leading up to the Second World War, Chris spent much of his childhood buffeted by the conflict engulfing his country. His family participated in the resistance against both Soviet and Nazi adventurism, with his mother working in the underground and his father eventually joining the Allied forces in the North African theater. It was several years before his mother, fearing forced exile to the Soviet Union, escaped from Poland with her children, finally being reunited with Chris’s father in England.
To know this multidimensional person fully, it is helpful to know how he began life. Born Krzysztof Jan Michejda to a
After the war, Chris’s family moved to Chicago. As a B.S. degree candidate at the University of Illinois, Chris got his first
10.1021/tx700056k CCC: $37.00 © 2007 American Chemical Society Published on Web 03/03/2007
324 Chem. Res. Toxicol., Vol. 20, No. 3, 2007
research experience working with the renowned organic chemist, Kenneth Rinehart. After coauthoring two papers with him during his undergraduate years, Chris enrolled in the Ph.D. program at the University of Rochester under the mentorship of National Academy of Sciences member D. Stanley Tarbell. There, he received further thorough grounding in the fundamentals of organic chemistry, including basic research in synthesis and mechanism studies. It was in Rochester that Chris met the love of his life, Maria Lacki. Maria was newly arrived from Poland as a Fulbright Fellow, with an MD degree, to become a resident at the university’s hospital. Chris, being perfectly bilingual and seeing a wonderful personal opportunity in her advent, helped Maria adjust to life in the United States and eventually persuaded her to marry him. Thus began a lasting partnership, both personally and professionally. Chris continued on as a chemistry scholar, and Maria became an eminent researcher in her own right, specializing in techniques for corrective prenatal surgery and studies of fetal stem cell biology. They loved to travel together, with Chris often boasting that he was attending the “wives program” (as the accompanying person’s activities were called in those days) at Maria’s professional meetings. Following his Ph.D., Chris took a postdoctoral appointment at Harvard working with Paul Bartlett before moving to a faculty position at the University of Nebraska in Lincoln. He rose through the ranks there to become Full Professor, taking time out for a sabbatical stay at the Swiss Federal Institute of Technology in Zurich with Nobel Laureate Vladimir Prelog along the way. His research during those early days focused on characterizing the fundamental physicochemical properties of exotic species such as triazenes and tetrazenes, with emphasis on the mechanisms of their radical and nonradical dissociation reactions. It was in Zurich that Chris cemented his commitment to research at the interface of chemistry with biology. In 1976, Chris left Nebraska to become Program Director for Chemical Dynamics at the National Science Foundation (NSF) in Washington, DC. Two years and many contacts later, he joined the research operation at the National Cancer Institute’s (NCI’s) Frederick, Maryland, campus at the invitation of the noted cancer researcher, William Lijinsky. At NCI, Chris’s attention turned increasingly to using his basic research findings in chemistry to address problems in biology. His first landmark publications on the chemistry of the carcinogenic nitrosamines appeared in 1976, providing new insights into the mechanisms of cancer causation. He made seminal contributions to our understanding of the chemistry of dialkylamino radicals through characterization and elucidation of their properties as well as those of their precursors. At the time, little was known about these radicals, which he realized were possible products of biological amine oxidation. His group’s demonstration that neighboring group participation was involved in the solvolysis of both R-ureido- and β-tosyloxy-nitrosamines led to his hypothesis that sulfation of β-hydroxynitrosamines could lead to their activation. He tested this hypothesis by investigating the mechanism of carcinogenic activation of 2-hydroxyethylmethylnitrosamine, an environmental carcinogen. Further collaborative work quantified labeled nitrogen production in the metabolism of several nitrosamines, leading to the conclusion that there are other metabolic paths. Chris also demonstrated that the metabolic activation of methylphenylnitrosamine produces the benzene diazonium ion as expected but that this goes on to form triazene adducts with bases in DNA. His early work and his nitrosamine research led him naturally to consider and develop triazene derivatives as effective
Editorial
antitumor agents. Exploiting his knowledge of fundamental triazene chemistry by predicting and then confirming the activity of such compounds as mutagens, he worked further to design potential cancer chemotherapeutics based on the chemistry of their action as DNA alkylating agents. He was deeply involved in the medicinal chemistry of anticancer drugs and pioneered the development of small-molecule toxins targeting cell surface receptors capable of selectively eliminating cancer cells without harming normal cells and tissues. His research also focused on designing inhibitors of HIV-1 reverse transcriptase as potential treatments for AIDS. His collaborative work with researchers from other institutions led to the discovery of an antiproliferative factor as a causative agent of interstitial cystitis and to development of a new class of highly selective phosphatase inhibitors that are potently active against liver cancer in animal models. Most recently, he and his co-workers discovered a rational approach to specific inhibition of integral membrane proteins that has led to the development of promising novel drug candidates. His group’s pioneering work with bisimidazoacridones resulted in a new class of compounds potently cytotoxic to liver and pancreatic cancers as well as leukemias; one of these agents is currently being readied for proposed clinical trials as a treatment for gastrointestinal cancers. Chris possessed a unique combination of attributes that contributed to his extraordinary success as a promoter of interdisciplinary communication and research. First of all, he had an amazing breadth of interdisciplinary understanding. There was essentially no subject that he could not discuss knowledgeably, from hardcore theoretical/computational chemistry to the intricacies of molecular signaling mechanisms. Perhaps more important, though, was Chris’s especially engaging personality. He combined a disarming sense of humor with an ability to make everyone he met feel welcome in his presence. With new acquaintances and old friends alike, he asked aboutsand rememberedsdetails of their personal as well as professional interests. It was clear that he cared about the whole person, not just the scientist. As a people person who was at the same time a noted researcher, Chris was a leader in getting people with complementary knowledge and skills together for interdisciplinary dialogue. He was intimately involved in establishing both the American Chemical Society’s (ACS’s) Division of Chemical Toxicology and the Chemistry in Cancer Research (CICR) Working Group of the American Association for Cancer Research (AACR). As a CICR steering committee member, he participated in planning its highly successful first scientific meeting held in February of this year under the joint sponsorship of the AACR and the ACS. He was a member of the Editorial Board for Chemical Research in Toxicology. He was Associate Editor of Cancer Research and served on the Editorial Boards of two AACR journals, Molecular Cancer Therapeutics and Cancer Epidemiology, Biomarkers, and PreVention. At the NCI, he founded and chaired the Chemistry and Structural Biology Faculty for NCI’s Center for Cancer Research (CCR). He headed the Molecular Aspects of Drug Design Section of CCR’s Structural Biophysics Laboratory and worked hard toward the goal of bringing a Program in Chemical Biology into being. In parallel with his tireless efforts at the interface between chemistry and biology, Chris was a paragon of citizenship, both in the United States and in the country of his birth. As an American who had maintained close contacts with similarly influential individuals in Poland, Chris was a frequent participant in high-level discussions of Polish-American relations at the White House and elsewhere, especially during the rise of the
Editorial
Solidarity movement. In honor of these and other notable accomplishments made by Chris and Maria Michejda, they were awarded the coveted Knight Cross of the Order of Merit of the Republic of Poland in 2005. Symbolic of Chris’s dedication to his homelands as well as to his mentorship and scientific goals, a scholarship fund has been created in his name whose purpose is to sponsor postdoctoral opportunities for young Polish medicinal chemists to study in the United States. Chris was a beloved mentor for a great many undergraduate, doctoral, and postdoctoral fellows who have gone on to prominent positions during his lifetime. This new fellowship, administered by the Kosciuszko Foundation in New York, will continue his legacy of providing for future generations of leaders, even after his death. Chris’s untimely demise came as he was racing from one important opportunity for interdisciplinary dialogue to another. While saying goodbye to colleagues at the dinner break for CCR’s annual Principal Investigator Retreat in Maryland on the way to a high-level meeting aimed at formulating a plan of
Chem. Res. Toxicol., Vol. 20, No. 3, 2007 325
action for curing cancer to take place the next day in Michigan, he suddenly collapsed and could not be revived. He is survived by his wife Maria, their daughter Monika and her husband Bob Goodrich, the Michejda grandchildren Gabriella and Andrew Goodrich, and Chris’s brother Albert and his family. We join Chris’s loved ones in mourning the loss of this very special person. A web site inviting and publicizing personal tributes to Chris Michejda has been established at http://web.ncifcrf.gov/news/ michejda_quotes.asp.
Nadya I. Tarasova, NCI at Frederick Richard N. Loeppky, Chemistry Department, University of Missouri R. Andrew Byrd, NCI at Frederick Larry K. Keefer, NCI at Frederick TX700056K
