A Tribute to John Doull,BS,PhD,MD: Scientist,Physician,Educator,Communicator,Advisor,and,Above All,A Gentleman and Friend to Many

John Doull, BS, PhD, MD (1922-2017), a leader in the science and practice of toxicology and human safety and risk assessment for over two-thirds of a century, passed away on March 24, 2017, in Olathe, Kansas, at 94 years of age after a brief bout with cancer. John was born on September 13, 1922, in Baker, Montana, to John G. and Vivian (Kelling) Doull. John’s father had immigrated to the United States from Scotland, served in the US Army in World War I, and became a successful business owner. John’s mother was from Iowa. John is survived by his wife, Vera Mae (Orsborn), who he married on March 1, 1958; his children, Ellen Jane Winter, John Kelling Doull, and James Douglas Doull and their spouses; 11 grandchildren and 5 great-grandchildren; and by innumerable friends around the globe and from all walks of life who had the good fortune to know John. John was a man of deep Christian faith that served as the foundation of his humility, his drive for excellence in all he did, and for his genuine love of people. He lived his life to the fullest with his wonderful wife, Vera, and family and had immense impact on the field of toxicology and how the results of toxicologic research are used to inform major policy decisions that protect and promote the health of human kind.

Figure 1.

John and Vera Doull, photographed at the 2012 Society of Toxicology Annual meeting. Photo credit: Kimberly Klaassen Lindemann.

John was a true son of the Great Plains in the Midwestern United States. He lived his life in a geographic triangle with vertices anchored in far eastern Montana where he was born and grew up, Chicago, Illinois, where he received his professional education and began his highly productive career at the University of Chicago Medical Center where he would spend 21 years, and the Kansas University Medical Center (KUMC), Kansas City, KS. With KUMC and Eastern Kansas as his home base, his career would extend for more than an additional 50 years and be marked by extraordinary contributions as a scientist, physician, educator, communicator, and scientific advisor on health issues of global concern and impact.

John was born and grew up on one of the last frontiers of the United States. The small community of Baker, Montana, where he was born came into being as a “watering stop” for coal-fired, steam locomotives on the Chicago, Milwaukee, St Paul, and Pacific Railroad, often referred to as the Milwaukee Road, constructed in the late 1800s and early 1900s. The small towns, farms, and ranches of the area were populated to a large extent by immigrants from Northern Europe, Scandinavia, Scotland, and Ireland with many having arrived via Canada. It was a difficult area for growing traditional crops like grains without irrigation because the precipitation did not measure up to the promise of land promoters. It was a land of wide open spaces populated by a few hard-working folks. I learned of the area first from one of my grandmothers who had homesteaded in western South Dakota in the late 1800s.

As a youngster, John moved west with his parents on the Milwaukee Road to Miles City, Montana, where he graduated from Custer County High School in 1940. Students of US history will recall the county’s namesake—General George Custer and his defeat in the epic Battle of the Little Big Horn on July 25 to 26, 1876, near where John grew up. After high school graduation, John headed further west on the Milwaukee Road to Bozeman, Montana, where he attended Montana State College (MSC), now Montana State University, and received his BS in Chemistry in 1944. He then entered the US Navy serving as an Electronic Technician Mate Second Class on the battle ship, US New Jersey in the South Pacific.

With his service in World War II (WWII), John became a part of what the US Journalist Tom Brokaw, a native of a small town in South Dakota, wrote—“it is, I believe, the “greatest generation” any society has ever produced.” Brokaw ¹ noted these men and women fought not for fame and recognition but because it was “the right thing to do.” This short phrase, “the right thing to do” would aptly describe one of the principles that guided John Doull’s life and professional career.

The University of Chicago Years

With his formal military service over in the fall of 1946, John headed east on the Milwaukee Road to Chicago, Illinois, and the University of Chicago (UC). One of his professors at MSC knowing of John’s interest in biochemistry had arranged an interview with Dr George Mangum, a former MSC graduate who was the director of the UC Toxicity Laboratory and a professor of biochemistry. Professor Mangum suggested that John pursue studies in pharmacology and work with Dr Kenneth Dubois who became John’s advisor, colleague, and good friend. ² The UC Department of Pharmacology was created in 1936, and Dr Eugene M.K. Geiling was named the department’s first chair. A paper authored by Doull ³ published in the Annual Reviews of Pharmacology and Toxicology entitled “Toxicology Comes of Age” contains John’s recollections of some of the people and events that influenced his own career and the development of toxicology as an academic discipline. Later in this tribute, I will sometimes refer to it as John’s “recollection treatise.” His paper should be read by all toxicologists. In my opinion, it is a wonderful account of the early days of building one of the key foundations for the field of toxicology. John had a remarkable role in creating that 20th-century foundation beginning at UC and, equally as important, in building a bridge to toxicology as we know and practice it today in the 21st Century.

To provide context for John’s experiences at the UC, some background will be useful. The UC was a relatively new private educational institution with roots traced to the late 1800s and the early 1900s. Its medical school was not established until 1927. The UC, by WWII, was becoming recognized nationally and globally as a leading educational institution with a very strong reputation in several fields, including the sciences and medicine. The UC attracted a very eclectic assortment of faculty and students. Among them were some of the best students from the Midwestern part of the United States.

The UC had a key role in the beginning of the nuclear age as one of the cornerstones of the Manhattan Project, the secret US military project to develop an atomic bomb. The UC unit of the Manhattan Project operated under the code name, the Metallurgical Lab. Dr Enrico Fermi and his team created the first controlled, self-sustaining nuclear chain reaction on December 2, 1942, underneath the stands of Staggs field at UC. Dr Glenn Seaborg, usually identified with the University of California–Berkeley, conducted pioneering work in laboratories at the UC Metallurgical Lab when he isolated and measured the newly discovered Plutonium-239. It would be the key component used in the first atomic bomb detonated in July 1945 at the Trinity Site near Alamogordo, New Mexico. The subsequent bombing of Hiroshima and Nagasaki, Japan, in August 1945 was a key to ending WWII in the Pacific. It ended John’s formal military service in 1946.

The work at the UC during WWII gave rise after WWII to the Argonne Cancer Research Hospital within the UC medical center, where pioneering work would be conducted on cancer therapy and hematopoietic diseases. The UC would also become the operator of the Argonne National Laboratory built west of Chicago. Both were funded by the newly created US Atomic Energy Commission, which would succeed the Manhattan Project. Not as widely known as the nuclear research activities was early work in pharmacology and toxicology conducted at UC. As part of US National Defense activities, the University of Chicago Toxicity Laboratory was created in 1941 to evaluate potential chemical warfare agents and antidotes. With the experience of the use of chemical warfare in World War I still a fresh memory and war clouds on the horizon, the United States needed such a laboratory. The first official investigator was Dr Eugene M.K. Geiling, a pioneer in pharmacology and comparative toxicology, who John would come to view as a highly influential mentor.

Jumping ahead, in 1945, the Toxicity Laboratory became a part of the US Army Chemical Warfare Service. Between 1947 and 1950, the laboratory operated under a contract with the US Atomic Energy Commission, the successor to the Manhattan Project, focusing on the toxicity of critical metals used in nuclear activities ⁴ and the medical effects of ionizing radiation. The name of the laboratory was changed to the UC US Air Force Radiation Laboratory. Dr Julius Coon became the director and was succeeded by Dr Ken DuBois in 1953 who served until his death in 1973. ² Shortly thereafter, the laboratory closed. John was a research assistant in the Laboratory during 1946 to 1950 while conducting his PhD studies and research.

John was indeed fortunate to have the UC as his home for his graduate and professional studies and early academic career. It had a huge influence on his career. John’s PhD thesis spanned from basic chemistry to physiologic and pharmacologic effects in intact organisms. It described the cardiotoxic and other effects of bufagin that was obtained from the parotid gland of the giant toad Bufo Marinus and labeled by feeding the toads ¹⁴ C-labeled algae. ^5-6 In my opinion, this would still be an elegant thesis if it were submitted today. With receipt of his PhD in pharmacology, he became a research associate in the Toxicology Laboratory. As a graduate student and research associate, he also conducted seminal research on the acute and chronic toxicity of organophosphate (OP) insecticides. ^{7 -9}

In his recollection treatise, John described with affection his relationship with Geiling as a patriarchal department chair and benevolent advisor. He noted that during a fateful breakfast, Geiling and he discussed John’s going to medical school. When John indicated that he would like to think about it, Geiling suggested that he do so quickly because Geiling had apparently already enrolled John in a gross anatomy class starting the following week. Later, John would note that while participating in gross anatomy laboratories, he began wearing his trademark bow tie; it had advantages when working over cadavers compared to a traditional long tie that frequently drooped. John received his MD degree from the UC in 1953.

Beginning in 1954 and continuing until 1967, John served as the assistant director of the UC US Air Force Radiation Laboratory working closely with his friend, Kenneth DuBois, who served as director. ² In 1956 to 1957, John concurrently served as an assistant professor in the UC Department of Pharmacology and from 1957 to 1967 concurrently served as an associate professor in the same Department. In that era, he and his colleagues conducted some landmark studies on radiation effects and radioprotective agents. ^{10 -15} John was later to recall these as “golden years.” In his recollections treatise, he noted many of the PhD students, postdoctoral fellows, and faculty who were associated with the laboratory. It is quite literally a list of “who’s who” in the early years of toxicology; they were builders and leaders of the new emerging discipline of toxicology.

When viewed from a long-term perspective, institutions, like individuals, have a life cycle and are constantly changing. This was true of the Toxicity Laboratory and its successor organization and the UC as a whole in the 1950s and 1960s. In this era, many organizations were seeking to capitalize on strengths developed during WWII and create strategies for their future. John noted that Dr Leon Jacobsen, the Dean of UC Biological Sciences in the 1960s, was interested in shifting away from studies that focused on whole animal responses to those that focused on DNA. This strategic change essentially sealed the fate of the Toxicity Laboratory. With the change in the institutional environment at the UC, it is not surprising that John began to seriously consider other career opportunities in toxicology at other institutions that were regularly being presented to him.

As I noted earlier, John married Vera Mae Orsborn on March 1, 1958. By 1967, the family had expanded to include their daughter, Ellen Jane, and twin sons, John Kelling and James Douglas. I am sure in considering any potential relocation, a family-friendly environment with access to good schools was high on John and Vera’s priority list. As an aside, they would also need a home that could accommodate the organ that was a fixture in that household. Among his many skills, John was an accomplished organist.

My Life-Long Friend and Mentor

Before continuing, let me briefly digress and recount some of my own interactions with John. Early in my career my principal mentor, the late Leo K. Bustad, emphasized the importance of knowing significant scientific achievements, when they occurred, who was involved, and where these activities occurred. This is embodied in the quote from William Shakespeare engraved on the National Archive Building in Washington, DC—“What’s past is prologue.” It was in this spirit that I began to visit in the early 1960s some of the significant laboratories involved in my principal research interests at the time—the health effects of ionizing radiation and especially internally deposited radionuclides.

One of my earliest visits was to Argonne National Laboratory and the UC in the fall of 1960. Such visits were usually preceded by a few calls to Bustad’s extensive contacts at the institutions I was to visit. At the UC, the contacts included John Doull and Dr. Leon Jacobsen (a son of Norwegian immigrants whose roots traced to North Dakota), he would receive his MD from UC in 1939 and would ultimately serve as Dean of the UC Biological Sciences, Director of the Argonne Cancer Research Hospital, and Dean of the UC Medical School). What a visit I had! I was greeted as a friend and colleague. The discussions were broad ranging and stimulating and, for a young scientist, very encouraging as to career prospects. As I recall, John and I, early in the visit, explored some of our common roots, including his life on the Milwaukee Road. I noted my own use of the Milwaukee Road, with travels going to and from my home, starting in 1944, in Richland, Washington, adjacent to the Hanford Nuclear Site through Bozeman, Miles City, and Baker, Montana, to Southwest Minnesota where I spent the summers of 1946 to 1949 with my grandparents.

At the time, John and his colleagues were conducting research on radiation effects in rodents and searching for potential radioprotective agents. I was studying the effects of ingested radiostrontium in miniature pigs. We compared notes on critical hematologic effects of bone marrow irradiation, including the pathogenesis of hematopoietic neoplasms. These discussions were a natural prelude to discussions that followed with Professor Leon Jacobsen, a world-renowned figure in the field of hematopoietic effects of radiation. Leon was the sole physician present when Enrico Fermi’s team demonstrated the first self-sustaining nuclear chain reaction at the UC. Jacobsen, in turn, introduced me to Dr. Eugene Goldwasser, a UC biochemist. Jacobsen and his team had previously identified, in whole animal studies, the kidney as a source of an erythropoiesis-promoting agent. Goldwasser would later identify that agent as erythropoietin, which the biotechnology firm, Amgen, would later commercialize. As an aside, to the chagrin of Goldwasser, the UC never filed the patent application relating to discovery of erythropoietin. I returned from the visit with a small sample of semipurified erythropoietin for use as a control material in my own studies. Of much greater significance, when I left the UC, I knew I had a new friend and mentor, John Doull. What I did not know was the breadth of our mutual interests and John’s influence in so many different ways on my career over the next 57 years.

In 1960, John was already a member of a number of scientific organizations. During my visit, we compared notes and determined that I was also a member of several of these organizations, including the Radiation Research Society and the American Association for Advancement of Science. John suggested I might consider joining several other scientific organizations, including the American Society for Pharmacology and Experimental Therapeutics (ASPET). He understood the importance of scientific societies as a base for networking with fellow scientists.

I followed John’s advice and attended the 1961 ASPET meeting held in Rochester, New York. My mentor had arranged for me to also visit as a prelude to the ASPET meeting, the University of Rochester (UR) Department of Radiation Biology and Medicine, whose origins traced to the WWII Manhattan Project and the conduct of pioneering inhalation studies. During that visit, I met many individuals who were leaders in the field of radiation toxicity. This included Drs. Harold Hodge, Paul Morrow, and Louis Casarett. ² These individuals would become leaders in the emerging field of toxicology. Harold Hodge, who was then Chair of the UR Department of Pharmacology, noted that he would be chairing a special meeting held in conjunction with the ASPET meeting as a step toward creating a new entity—the Society of Toxicology (SOT)—and urged me to attend. I did so. When I walked into the large lecture hall, 2 individuals from among a sea of strangers greeted me—John Doull and Louis Casarett. For a 24-year-old scientist that was a special treat! As an aside, although I signed the list of attendees at the meeting, I did not feel my credentials measured up at that time for full membership in the SOT. It would be several years before John Doull and Paul Morrow sponsored my application for full membership in the SOT. This was just one of many endorsements and encouragements John would give me over the decades.

Kansas University Medical Center Years

In the spring of 1967, John Doull accepted Dr. Edward Walaszek’s invitation to become a Professor of Pharmacology and Toxicology at the KUMC in Kansas City, Kansas. The KUMC wanted to build on its traditional strength in pharmacology ¹⁶ and increase its capabilities in the emerging field of toxicology. The 45-year-old Midwesterner from the UC, John Doull, was selected to lead the effort. What a great and impactful decision on the part of the KUMC! John left his upper Midwest anchor points on the Milwaukee Road and headed south. He was later to note that leaving Chicago, still suffering from the aftermath of a record snowfall and arriving in eastern Kansas with rolling hills and with flowers blooming, seemed like a good omen. Indeed, it was a good omen for John, his family, KUMC, and the field of toxicology. During the next half century he guided the development of a world class center in Toxicology within the KUMC. For 50 years, KUMC and Kansas served as John’s home base as he influenced how toxicological research was conducted and how the results would be used to inform safety and risk assessments directed toward protecting and improving human health around the world.

In his recollections treatise, John gave generous credit to his colleagues at KUMC for their role in the development of pharmacology and toxicology at the KUMC. This acknowledgment was not surprising, since John was always generous in acknowledging the contributions of others and quite humble in acknowledging his own role, in any activity. In particular, he noted the contributions of Drs. Ed Walaszek, Daniel Azarnoff, Aryeh Hurwitz, Stata Norton, Curtis Klaassen, and Karl Rozman. It is noteworthy that during John’s early tenure, the department changed its name from Pharmacology to Pharmacology, Toxicology, and Therapeutics. He noted that was actually a transcription of a previous name adopted by the Department in 1909 and abandoned in 1926. I am confident that John felt very comfortable with this 3-legged stool recognizing his own interest in all 3 areas.

Indeed, it is my opinion that one of John’s important attributes throughout his career was his ability to focus on using the best available scientific information to inform decisions on important matters whether it be the diagnosis and treatment of a patient, the health impact of some agent on a population, the safety of a new pharmaceutical or a pesticide, or the use of science to inform development of a new regulation to protect and promote human health. He was able to look beyond labels and individuals as to origin of information or assignment of credit and focus on use of the information. Perhaps bolstered by his superb education and training as a physician, John understood the importance of gathering all the relevant information, synthesizing it and then making a decision. He had a low tolerance for individuals deciding on their desired outcome and then assembling the facts to support that conclusion. He also had a low tolerance for omitting facts and regularly called attention to one of the inscriptions carved into the base of the Albert Einstein statue in front of the National Academy of Sciences building in Washington, DC. The inscription is “The right to search for truth implies also a duty; one must not conceal any part of what one has recognized to be true.”

Educator and Mentor to Many

It is a challenge to review in a succinct manner John’s professional career that spanned over seven decades from 1946 until his death in 2017. Traditionally, for a scientist, one starts a discussion of their contributions with a review of the individual’s body of scientific work covered in their publications. In John’s case, I think it more appropriate to start by commenting on his role as an educator and mentor.

My own experience with John as a teacher and mentor has been mirrored by the experience of numerous other individuals. I know of no other individual in the field of toxicology who has had such wide personal influence on many others. It would be incomplete to say John was very approachable because, oftentimes, he would approach others and initiate the interactions. Many individuals at the UC and KUMC had the good fortune to have him as a teacher. A hallmark of John’s role as a university professor was to lead by humble example. He was known for his accessibility to students at almost any time, and he demonstrated on a daily basis the virtue of plain hard work and dedication to task. This was fueled, in part, as a former graduate student recalled, by his consumption of huge quantities of coffee from a coffee station located conveniently just outside his office door! It was commonplace to see John in his office or strolling the main corridor of the Department late into the evening. And John and Vera never missed a graduate student/postdoc social gathering where they demonstrated genuine interest in individuals that went beyond the superficial. Not surprising, a substantial portion of those students and postdoctoral fellows sought out one-on-one interactions with John who was remarkably available and whose office door was almost never closed. He was a great listener and insightful advisor. Most importantly, he fully appreciated the many roles individuals can fill and have a productive and enjoyable career. He viewed “success” as a description of a journey, not as a destination.

Until very recently, John, frequently accompanied by Vera, were regular attendees at SOT meetings. It was always a treat to visit with him and hear his views on contemporary issues, not just in toxicology, but other issues on the world stage. I know he attended some scientific sessions, however, he could usually be found in the corridor surrounded by friends. He was always especially pleased when the circle included students and young scientists; John was always looking to the future and doing so with optimism.

Many of the individuals John helped educate and guide have gone on to highly productive positions in academe, industry, and government—a true tribute to John and others who helped those individuals early in their careers. The list goes well beyond the numerous graduates of programs at the UC and KUMC. Many individuals have followed John’s example and became leaders in professional organizations and in advisory roles.

His Publication Legacy

Let me now return to the traditional approach to considering John’s publication legacy. One typically starts by reviewing the publications they have authored or coauthored starting with the books they have edited or coedited followed by papers they have authored or coauthored in peer-reviewed journals, followed by technical reports, perhaps, a listing of Key Committee reports they helped prepare and, maybe, concluding with key talks the individual has given. For a few scientists, I have seen a list of a dozen or so texts and over 1000 peer-reviewed papers. Quite frankly, I have wondered as to the actual role of some of those “senior authors” in conducting the research and preparing many of those papers. In John’s case, I am confident there is no padding of his curriculum vitae. Indeed, for John’s peer-reviewed research publications I am impressed with the shared authorship; John understood the importance of team work in conducting and reporting research. Moreover, John was not one to seek center stage. In all of my dealings with him on authorship matters, I found him quick to recognize his colleagues, especially junior colleagues.

As I reviewed John’s publications, I was pleased to note a number of them that summarized the status of the field of toxicology and its linkages to safety and risk assessment. ^{3,17 -21} These papers were useful at the time they were prepared and will continue to provide insight for decades to come. I wish he had written even more. In this vein, I also recall many of our conversations during the last decade. Common themes of those conversations were (a) the distinction between safety, hazard and risk, and (b) the potential contributions of whole animal studies, epidemiological investigations, and studies focused at the molecular and cellular levels of organization to understanding hazard and risk. Both of us recognized the value of each kind of study but lamented the extent to which one approach was increasingly being pitted against another.

John’s education as a physician instilled in him an appreciation of the complexity of disease in individual patients and the critical role of a differential diagnosis in assigning causality. As a physician and animal researcher, starting in the late 1940s, he understood the concept of “biomarkers” before it became a fashionable part of the vocabulary of toxicologists and risk assessors. John recalled that when he returned to the UC in 1991 to receive the UC Distinguished Medical Alumnus Award, one of his influential mentors, Leon Jacobsen, recalled that in retrospect he (Jacobsen) had probably made the wrong decision for the UC in the early 1960s regarding the merits of whole animal studies. Jacobsen, as a leader in developing the UC research strategy, had deemphasized them in favor of studies at the cellular and molecular level.

I suspect on hearing Jacobsen’s comment, John smiled and recalled his own experiences. This included his PhD thesis on radiolabeled bufagin, its effects on respiration of cardiac muscle and the numerous studies he and his colleagues had conducted using whole animals in the Toxicity Laboratory as they investigated the newly discovered OP compounds. Without fanfare, he probably also quietly recalled to himself the pioneering work of Jacobsen, Goldwasser, and others at UC leading to the discovery of erythropoietin, its commercial development by Amgen and its role in treating patients. This was clearly a seminal discovery grounded in human observations, animal studies, and fundamental investigations at the cellular and molecular level of organization. It was an approach John Doull felt very comfortable advocating.

Casarett and Doull: A Major Legacy

Without question, one of John’s most lasting contributions to the science of toxicology was his role in developing the now classic textbook, “Toxicology, The Basic Science of Poisons”. ²² In the late 1960s, I served with John and Louis Casarett on the Toxicology Study Section (TSS) of the National Institutes of Health. During the TSS meetings, and at many other meetings, the participants would regularly lament the need for a comprehensive textbook covering toxicology. It was at one of the rump sessions to one of the TSS meetings that John and Lou took up the challenge and “hatched up” the idea for the now classic textbook. A brief description of the origins of textbook is contained in a piece written for the 50th Anniversary of the SOT by Lou’s close colleague at the UR, Paul Morrow, Lou’s wife, Margaret Bruce and John. ²³ The fine-tuning for the first edition and its contents and selection of chapter authors occurred during a summer visit of John and his family to Hawaii where Lou had relocated from the UR. Unfortunately, Lou passed away before the first edition was completed. I still recall how pleased I was when John asked me to use Louis’ notes and complete the radiation toxicology chapter. As I recall, he told me it was “my duty”; words John only used occasionally when he had to make a “hard sell.” I wisely enlisted my colleague, Charles Hobbs, to assist me in fulfilling “my duty” by authoring the chapter on Radiation Toxicity in the first edition of Casarett and Doull. ²⁴

The most recent editions of Casarett and Doull have been very ably edited by Curt Klaassen ²⁵ who John recruited to the KUMC. Ironically, the recruitment coincided with John’s service on the TSS which evaluated several of Klaassen’s grant proposals. As I recall, John recused himself at the appropriate times in the TSS deliberations on Klasssen’s proposals. Since the first edition of Casarett and Doull was published in 1975, thousands of individuals around the globe have used it to gain their basic education in toxicology; a remarkable legacy to John and his good friend and coeditor, Lou, and to Curt Klaassen. The textbook is now in its 8th Edition. ²⁵ It is appropriately dedicated to John.

Service in Professional Organizations

During his long and distinguished career, John, as a member and, most importantly, as a leader, provided valuable service to more than a dozen major national and international organizations. He initially joined the American Chemical Society in 1949 (recall he received his BS in Chemistry from MSC) and soon after joined the American Industrial Hygiene Association, Radiation Research Society, ASPET, Society for Experimental Biology and Medicine, New York Academy of Sciences, and the American Association for Advancement of Science (AAAS). In 1958, when 36 years old, he was recognized as an AAAS Fellow.

He was a Founding Member of the SOT in 1961. He served the SOT in many roles, including through the succession of offices leading to SOT President in 1986 to 1987. He was also a member of the Academy of Toxicological Sciences (Fellow—1999), American Academy of Clinical Toxicology (Fellow—2006), the Canadian Academy of Clinical Toxicology, the Toxicology Forum, the American Board of Toxicology (ABT), the American Water Works Association and the American Conference of Governmental Industrial Hygienists. John believed strongly in the importance of belonging to scientific organizations and, most importantly, serving the organizations by providing leadership.

John’s role in organizing the ABT is especially noteworthy. He was one of a small group of well-recognized toxicologists who agreed to serve in 1979 as founding Board members for the new entity. Most importantly, John agreed to serve in the critical role as Chair of the first ABT Examination Committee. I am confident that the primary criterion for selecting John for this critical role was his stature in the field of toxicology. However, another factor is noteworthy. That is his early role in computer-aided education ²⁶ and the use of computer-based examinations. John had access, at the time the ABT was founded, to a treasure trove of computer-based examination questions on toxicology based on his decades of experience at UC and KUMC. As an aside, knowing that John was at the helm of the ABT Examination Committee was a key factor in my deciding to take the first ABT examination. I also decided to attend Curt Klaassen’s first Mid-America Toxicology Conference to help me prepare for the examination and gain some experience with those computerized questions. The first ABT examination was given on August 4, 1980, at 4 locations; Washington, DC, San Francisco, Indianapolis, and London. With passage of the rigorous examination, I joined several hundred other individuals as one of the initial ABT Diplomates. The ABT has over the decades become a global leader in certification of Toxicologists achieving stature; stature that is in part attributable to the leadership of John and other pioneers in Toxicology who recognized the value of an entity that would certify based on a rigorous examination and set their own interests in achieving immediate accreditation aside in favor of the broad interests and needs of the discipline.

Advisory Service

From very early in his professional career, John recognized the importance and, indeed, “his duty” to provide professional advice to both private and public organizations. These advisory services began in 1950 soon after he completed his PhD thesis and while still in Medical School, when he began providing consulting services to a company developing and marketing pesticides. That kind of service would continue for two-thirds of a century as he became increasingly recognized as a “go to” toxicologist when advice was needed on a wide range of societal issues concerning the health of human kind that needed to be addressed using the best available science. As best I can determine, in the United States he served on advisory committees for every federal agency concerned with environment and occupational health issues.

Early in his career, he served on high-profile committees that would have lasting impact on health and environmental research in the United States. He was a member of the Wooldridge Committee (1965) appointed by President Lyndon Johnson to advise on the future of the National Institutes of Health research activities and their management. The Wooldridge Committee’s report ²⁷ had enormous influence on NIH’s research strategy in the coming decades. He was a key member of the Committee chaired by Emil Mrak, ²⁸ a Committee whose recommendations strongly influenced the future regulation of pesticides. Emil Mrak, a food scientist at that time was serving as the Second Chancellor of the University of California-Davis campus. Mrak would later serve as the first chair of the Science Advisory Board of the newly created US Environmental Protection Agency.

Beyond the committees in individual government agencies in the United States and around the globe, John had an important role in more than 20 committees of the National Academies of Science, Engineering, and Medicine, under the National Research Council (NRC) umbrella, including Chairing the Committee on Toxicology (1987-1993) and 7 other NRC Committees. ²⁹ He served on more than a half dozen committees of the Department of Health, Education, and Welfare, now Health and Human Services, including the National Institutes of Health Toxicology Study Section (1965-1970) and the Second Task Force on Human Health and the Environment (1976-1977). This included chairing the influential Committee on Fluoride in Drinking Water (2003-2005). He was an influential member of the Committee on the use of third party toxicity research with human subjects of the Academies Science, Technology, and Law program. From 1976 through 1995, John served on 10 Advisory Committees for the US Environmental Protection Agency beginning with his appointment in 1976 to the new Agency’s Scientific Advisory Committee for the Federal Insecticide, Fungicide, and Rodenticide Act. Beginning in 1988 and continuing until 2012, he was associated with the International Life Science Institute’s Risk Science Institute, whose activities focus on bringing together individuals from the private sector, government, and academe to address complex risk science issues. This tripartite approach was one that John was very supportive of and comfortable in joining.

Many of the Committees John served on dealt with quite contentious issues at the interface of science and public policy and beginning in the 1970s involved the evolving art and science of risk assessment. I recall well serving with John on the National Research Council Committee on Risk Assessment of Hazardous Air Pollutants (1990-1993) which produced the report— “Science and Judgement in Risk Assessment.” ³⁰ As John was to note ²⁹ the NRC Committee was unable to resolve the issue of whether regulators should use the “best science” or “plausible conservatism” as the basis of risk assessment. John was instrumental in encouraging Adam Finkel ³¹ to lay out the argument for “plausible conservatism” and McClellan and Warner North ³² to lay out the argument for use of the “best science.” This was a typical approach for John. If the debate of an issue could not be resolved, then at a minimum, try to get the contrasting positions documented. John also served concurrently on the Presidential/Congressional Commission on Risk Assessment and Management (1990-1993) chaired by Gilbert S. Omenn. ³³ Both entities had been mandated by the Congress in the Clean Air Act Amendments and had substantial impact on the subsequent development of air quality regulations.

In the deliberations of both these groups and many others, John was a faithful discipline of 2 historic figures that influenced toxicology. The first was Publius Terentius Afer (295-269 bc) who in Andria (The Lady of Andros) suggested “moderation in all things.” The second was Paracelsus (1493-1541 ad) who provided the most venerable principle of toxicology, “the dose makes the poison.”

In my opinion, John was most comfortable using scientific knowledge to guide professional judgment on the safety of chemicals and other agents. As one moved away from the science toward policy guidelines and judgment, as required in risk assessment, John became decidedly more uncomfortable. When we served together, I usually attempted to forge a middle ground viewing the science as informing policy decisions required to develop guidance and regulations to limit health hazards and risks. John was a strong advocate of using all of the science whether it be from epidemiological investigations, controlled exposure human studies, research with laboratory animals or investigations using cellular and molecular systems. John, ^29,34 strongly deplored the practice of using labels such as carcinogenic, teratogenic, and so on, that provided potentially misleading yes-no answers to safety questions. John and I both made this point in our talks at the Colloquium on Scientific Advances and the Future of Toxicologic Risk Assessment: 50th Anniversary of the NRC’s Committee on Toxicology, National Academy of Sciences, Washington, DC, December 1997. ^29,35

John was always an especially welcome member of any advisory group because of the breadth, depth, and richness of his experience as a basic scientist and his clinical experience in diagnosing and treating disease in human patients. He truly understood the complexity of disease, including cancer. No doubt, his views on these matters were further reinforced when he was diagnosed in 1989 with kidney cancer which was successfully treated.

John noted that one of the advisory activities he most enjoyed was that of the Threshold Limit Value (TLV) Committee of the American Conference of Governmental Industrial Hygienists. He served as Chair of the Committee from 1990 to 1998 and guided substantial improvements in the documentation undergirding the TLVs for specific agents. ^18,34 He also was a catalyst for developing closer ties to the German Maximale Arbeitzplatz Konzentretion (MAK) Commission. These activities were facilitated by his long-time KUMC colleague, recently deceased Dr Karl Rozman, and German friend, Dr Helmut Greim.

John also noted with pleasure his service starting in 1977 on the Flavor Extract Manufacturing Association (FEMA) Expert Panel that grew out of the 1958 Food Additives Amendments in which the concepts of preclearance and safety in use for food additives were introduced. John was a strong proponent of the role of expert judgment at the core of the FEMA Expert Panel’s activities as several thousand flavors were evaluated. ³⁶ It was fitting that his retirement dinner from the Expert Panel was held at a Medici Castle near Florence, Italy, a testament to John as a true Renaissance man.

Beyond his service on many national and international advisory committees, John served as an advisor, both formal and informal for many advisory committees to academic units and research institutes. He was a key advisor to 2 institutions I served, the Lovelace Inhalation Toxicology Research Institute (ITRI; 1966-1988) in Albuquerque, NM and the Chemical Industry Institute of Toxicology (CIIT; 1988-1999). I recall when I sought his counsel on leaving ITRI and accepting a position as the third President of CIIT, he emphasized to me that it was “my duty” to the fields of toxicology and risk assessment. John obviously had great respect for CIIT, funded by the chemical industry, but operating in a highly independent manner. John could always be counted on to advocate for creating new scientific knowledge to address important societal issues irrespective of the source of funding for the research or where the research was conducted.

In my opinion, I think John especially appreciated involvement in advisory activities that focused on resolving important, but practical, issues concerning human health. Many of these Advisory Groups brought together individuals from academia, industry, and government. Such tripartite participation was at the core of many of his activities such as with CIIT and with the International Life Sciences Institute (ILSI). As a member of the ILSI Board through 2012, he helped guide its activities as ILSI built a platform for toxicology in the 21st Century. It is noteworthy that he was comfortable with individuals from all sectors. In this regard, he was a bridge builder between the various sectors of Society, always focusing on using scientific knowledge to address important issues. He was also very comfortable interacting with lay people who were not scientists, as much as with scientists, a tribute to his “small town” roots in Montana where his neighbors came from all walks of life. After John’s participation in an Advisory meeting at ITRI or CIIT, it was not unusual for a secretary, technician, or student to tell me that Dr Doull had stopped by and chatted with them. John clearly knew what made an organization “tick” and how to help make them “hum.”

Well-Deserved Recognition

John’s outstanding service and achievements were recognized by his receipt of numerous awards from many different organizations. In this Tribute, it is possible to only highlight some of his most significant Awards. The SOT, of which he was a founding member, and its various affiliates bestowed on John the Kenneth P. DuBois Award in 1985 (Midwest Chapter), Ambassador of Toxicology Award in 1991 (Mid-Atlantic Chapter), the inaugural John Doull Award in 1992 (Mid-America Chapter), the SOT Merit Award in 1993, and the inaugural SOT Founder’s Award in 2008. In 1989, he received the Rutgers University Samuel Kuna Award. The American Conference of Governmental Industrial Hygienists recognized him with the Herbert Stokinger Award (1992) and the Meritorious Service Award (1996). The US Armed Forces Epidemiology Board recognized him in 1990 with the Commander’s Award for Public Service. The International Society of Regulatory Toxicology recognized him in 1990 with its International Achievement Award. The University of Arkansas Toxicology Symposium Series presented John its Snider Award in 1994 and the American College of Toxicology presented him its Distinguished Service Award in 1996.

The CIIT, on the occasion of its 20th Anniversary in 1996, recognized him with its Founder’s Award. ³⁷ In 1996, he received an Honorary Doctor of Pharmacy degree from the University of Kuopio, Finland. The Toxicology Forum recognized him in 2002 with the Phillip Shubik Award. The National Academies of Science, Engineering, and Medicine in 2002 named him a National Associate for his service on many of its NRC committees. The American Academy of Clinical Toxicology awarded him the Academy’s Career Achievement Award in 2013. In 2013, he received the Mildred S. Christian Career Achievement Award from the Academy of Toxicological Sciences.

Most significantly, his Alma Mater, the UC, in 1991 presented him the Distinguished Medical Alumnus Award. The KUMC in 1992 presented him a Special Recognition Award for 25 years of distinguished service. It is noteworthy that he would serve the KUMC for yet another 25 years as a Professor Emeritus of Pharmacology and Toxicology.

Postlude

Over the decades, I, just as many others did, called on John regularly as a friend, mentor, and counselor. Whatever the issue, be it scientific or personal or a blend of the two, I could count on John for his wise counsel and guidance. He was remarkable in his ability to address complex issues without passing judgment. When one finished a long conversation on a tough issue with John one had to inevitably ask—“Why didn’t I think of that path forward?” John’s reply was usually to smile and say— “You did!” or “We did it together!”

My last conversation with John was 2 weeks before he passed away. I called to tell him that I and many others would miss him and Vera at the 2017 SOT meeting which would begin 2 days later in Baltimore. He noted that Curt Klaassen had stopped by earlier in the week and other friends had called. John and I had a wonderful long conversation recounting numerous interactions and mutual friends we had the pleasure of working with over more than a half century. It was a real treat to recall occasions that included Vera. This included a trip to St Petersburg, Russia with my wife, Kathleen, and I after the 10th International Congress of Toxicology meeting held in 2004 in Tampere, Finland. His love and caring for Vera was so obvious. They were a wonderful couple.

The last conversation I had with John was truly a walk down memory lane. As the conversation was drawing to a close, John offered some sage and heartfelt advice— “Enjoy the SOT meeting. Remember the science will always be changing. You can miss a few sessions. Be sure to spend time at the meeting with old friends and be sure to make some new friendships, especially with students who can benefit from your experiences. Friendships and families are what really count in life!” What a wonderful commentary on a life well lived and, as always, great advice from John’s heart.

In the days ahead, we will all certainly miss John. However, let us quickly move the cloak of sadness aside and rejoice in our memories of having shared some time with John on the path of life. We can all remember the important role he had in our lives and the model he provided for us. The science of toxicology is much richer today and the health of human kind around the globe better because of John Doull.