John Jacob Abel: The Fifth Horseman

The Early Years

George Abel, father of John Jacob, had immigrated to the United States from Germany’s Rhine Valley in 1854 and worked on the farm of another German immigrant, John Jacob Becker. George married Becker’s daughter, Mary, and on May 19, 1857, John Jacob Abel, the first of their eight children, was born on the family’s farm near Cleveland, Ohio (1–3). Instilled with German academic values, John showed talent even in elementary school. He graduated as the top student in the Cleveland high school system in 1876 and entered the University of Michigan (2–5). After three years, Abel left college for financial reasons and became a high school principal in La Porte, Indiana. He also taught mathematics, Latin, chemistry, and natural science (6). The following year he was appointed superintendent of the public schools, but he continued teaching math and science.

Abel had taken few science courses in college, but teaching sparked his interest in medical science (1, 3–5), leading him to read broadly and to begin thinking about opportunities for research and medical study, especially those afforded by the excellent faculties and facilities existing at the time in Germany. Abel decided to prepare himself by first completing his undergraduate studies at Michigan. He studied physiology, anatomy, and physiological chemistry under Victor Vaughn and Henry Sewell in the medical school, receiving the Bachelor of Philosophy degree in June, 1883 (3, 4, 6). That same summer, John married Mary Hinman, a graduate of Elmira College and teacher of composition, history, and civil government at La Porte High School. From the beginning, Mary encouraged her husband’s educational goals, and they used their combined savings for his subsequent training in science and medicine (3, 7, 8). As a stepping stone to Germany, John targeted the Johns Hopkins University, which had been founded only five years earlier and was modeled on the best German schools. In the fall of 1883, the newlyweds moved to Baltimore, where John became a graduate student in physiology under H. Newall Martin (3, 4, 6). Mary had also hoped to study at Hopkins but discovered the university did not accept women (3).

Throughout his productive year in Martin’s laboratory, Abel continued to focus on Germany. He aimed high. Carl Ludwig, in Leipzig, was the most influential physiology teacher of the nineteenth century and one of the outstanding physiologists of his generation. Abel’s association with two eminent physiologists (Sewall and Martin) helped him obtain a position in Ludwig’s laboratory (3, 4, 8). Before departing for Germany, however, Abel took the summer to work in the laboratory of Horatio Wood, Sr., who had published a highly regarded textbook describing drug actions and was professor of materia medica, pharmacy, general therapeutics, and nervous diseases at the University of Pennsylvania. Wood’s laboratory first introduced Abel to studies of drugs and therapeutics using animals (3, 4, 6, 9).

European Graduate Training

On August 28, 1884, the Abels sailed for Germany (4, 5). Throughout his sojourn in Europe, Abel struggled to define his career goals, oscillating between medical practice and biomedical research. He knew that as a horse-and-buggy doctor he could provide a stable income for his family. Nevertheless, from the age of fourteen, he had rebelled against his father’s advice to find a financially secure job, drawn by the desire (3) to “work out something a masterpiece of some kind, in the medical line that will help people along a little.”

In Ludwig’s laboratory, from 1884 to 1886, Abel investigated the depolarization of frog motor and sensory nerves following heat stimulation. Abel quickly discovered the vast research opportunities available in Europe and wanted to stay, but first he needed to strengthen his knowledge of biomedical science. He enrolled as a medical student, learning anatomy, chemistry, histology, pathology, and physiology from Leipzig’s outstanding professors. Importantly, he also attended lectures by the pioneering pharmacologist, Rudolf Bohm (3, 8). While John pursued his medical studies, Mary acquainted herself with the latest developments in the fields of nutrition and home economics and on March 26, 1885, gave birth to their first child, Gretchen (3, 7).

Abel recognized the importance of chemistry and its applications to medicine and physiology (6). He spent the 1886–1887 academic year in Strassburg, where Felix Hoppe-Seyler was gaining an international reputation in the new field of physiological chemistry. Abel’s fellow students nevertheless steered him toward Oswald Schmiedeberg, who was also skilled in physiological chemistry but had a better equipped laboratory and devoted more time to students. Under Schmiedeberg, Abel carried out research in chemical pharmacology, reinforcing his interest in the medical applications of chemistry (3). While in Strassburg, Abel also attended medical lectures in internal medicine, pathology, and infectious diseases. He supplemented these clinical skills in the summer of 1887 by attending clinics in Wurzburg and studying medicine and surgery in Heidelberg (8).

In the fall of 1887, the Abels returned to Strassburg, and their second child, George, was born the following spring (8). Abel attended lectures by Bernhard Naunyn, Hoppe-Seyler, and Schmeideberg, and he completed his doctoral requirements using his research project from Ludwig’s laboratory. In July, 1888, Abel presented his doctoral thesis to the Strassburg medical faculty and was awarded a Doctor of Medicine degree (3, 5). That same summer, Abel took steps to find an academic position in physiology, pathology, or pharmacology and therapeutics in the United States. Abel’s former mentor Horatio Wood was rather discouraging, advising that Abel must first become known as a lecturer and independent investigator. Moreover, academic posts were not lucrative. One could more easily earn $30,000 as a mediocre clinician than $5,000 as an academic physiologist (3, 8). Unfortunately, Abel’s next move was compelled by a personal tragedy, in October, 1888, when the Abels’ daughter, Gretchen, contracted poliomyelitis and died. Mary suffered from depression for several months thereafter, and John moved his family to Vienna, one of Europe’s great clinical centers. During the winter of 1888–1889, John buried himself in work at Vienna’s hospitals, where thousands of patients presented clinicians with examples of every type of human ailment (3). Lacking a job offer, Abel continued studying in Europe, but financing presented a problem (3). Just then, the American Public Health Association announced a competition for the best essay on “Practical Sanitary and Economic Cooking Adapted to Persons of Moderate and Small Means,” which came with a cash prize funded by Henry Lomb of Bausch and Lomb. Mary entered an essay, “The Five Food Principles Illustrated by Practical Recipes,” which was unanimously voted the best of seventy entries (7). The $500 Lomb Prize arrived in January, 1889, and made it possible for John to remain in Europe another year. Mary returned to the United States in the summer of 1889, with John expected to join her in December (3, 7). In the fall of 1889, he moved alone to Berne, Switzerland, to work with Marceli Nencki, a noted biochemist, and the experience was of such benefit that John and Mary decided to finance Abel’s work with Nencki into 1890. Abel credited the work in Berne for stimulating his life-long interest in the chemical aspects of pharmacology (3, 8).

Meanwhile, Mary’s award-winning essay set in motion her relationship with the American Public Health Association and Ellen Richards, one of the judges of the Lomb Prize and an instructor at the Massachusetts Institute of Technology. In November, 1889, Richards offered Mary $1,000 to operate the New England Kitchen in Boston for six months. The Kitchen, modeled after the public kitchens in Europe, was to develop and supply working-class Bostonians with nutritious, inexpensive, takeout food. Mary opened the Kitchen on January 24, 1890, allowing John to extend his stay abroad, again (3).

In the spring of 1890, the Abels, from both sides of the Atlantic, again probed their American contacts, inquiring about positions for John. Through Mary’s contacts, Abel received an offer of an assistantship at Harvard and a vague offer to assume some of Victor Vaughn’s physiological chemistry teaching duties at Michigan. He accepted the assistantship, hoping for some latitude in the scope of his research. Then, on July 15, 1890, Abel received another letter from Victor Vaughn, sweetening the Michigan offer. The chair in materia medica and therapeutics had recently become available, and Vaughn now offered the Michigan chair to Abel, along with the physiological chemistry responsibilities (3). Although Abel had not initially sought a career in pharmacology, Nencki explained that it was a broad field, could be approached from many points of view, and offered many research options. Abel was now in his early thirties, and having finally landed an attractive academic appointment, he reckoned that pharmacology might be a better choice, anyway. From Berne, he wrote to Mary (3, 10), “I know that I can make vastly more out of Pharmacology in the States.”

Nencki, Ludwig, Schmiedeberg, and Naunyn sent letters of reference to Michigan on Abel’s behalf, and the university’s board of regents approved his appointment with a starting salary of $2,000 (3). Abel enthusiastically accepted, gracefully withdrawing from the Harvard position. Then, he asked Vaughn to delay his start date until January 1, 1891, explaining that he needed to strengthen his experience in clinical practice and prescribing medicines. Vaughn granted the request, but Abel actually spent much of the fall of 1890 in the biochemistry laboratory of Edmund Drechsel in Leipzig (3). On his way home, Abel travelled to Berlin to observe Robert Koch’s tuberculin treatment, which was receiving international attention. It became the subject of Abel’s first lecture at Michigan (8).

Teachingat the University of Michigan

Upon his arrival in January, 1891, Abel expected a professorship but discovered that his official title was actually Lecturer in Materia Medica and Therapeutics. He accepted the lesser rank, which was customary for new appointments at Michigan, assured that he could be quickly promoted based on performance (3). At first, teaching occupied most of his time; he lectured six days a week to an audience of medical, dental, and pharmacy students. Abel transcended traditional materia medica and offered a modern pharmacology course with both lectures and pharmacological demonstrations using anesthetized animals (6, 8, 10). He rearranged the medical curriculum, postponing pharmacology until the third academic year to build on second-year courses in physiology and physiological chemistry. Abel also introduced two new laboratory-based graduate courses, both listing physiological chemistry as a prerequisite: one on the influence of certain drugs on the metabolism of tissue, and the other on the methods of modern pharmacology (3, 10).

In November, 1891, Abel organized a journal club of promising students whom he had identified from the junior class. Meeting every two weeks, the students discussed current therapeutic advances, reported on journal articles, and performed some experiments (10). From the day he arrived, Abel claimed (8) “[that any of his] energy that was not given to… students was devoted to research work and to arousing the enthusiasm of others for it.” And he started from scratch (3): “There was not a scrap of apparatus, not even a test tube, a flask, or a beaker.” The university regents authorized $900, and Abel built a small laboratory under the staircase leading to the medical school amphitheater. Within a month, he was performing chemical studies and animal experiments (10). By the fall semester of 1891, Abel had expanded his laboratory facilities and invited advanced students to conduct research on special topics under his supervision. In January, 1892, Abel was promoted to professor, at a salary of $2,200. In June, the regents approved another $600 for laboratory apparatus (10). Abel’s innovations at Michigan represent the introduction of modern pharmacology to the United States, although the regents did not officially change the department and chair titles to Pharmacology until 1942 (10).

Teaching at the Johns Hopkins University

While Abel worked in Michigan, President Daniel Coit Gilman of the Johns Hopkins University continued efforts to establish a world-class medical school. He had already hired William Welch, William Osler, William Halsted, and Howard Kelly to head the clinical departments (pathology, general medicine, surgery, and gynecology, respectively). Now, he needed equally outstanding scientists to chair the preclinical departments (8). In January, 1893, Osler wrote to Abel, asking what it would take to attract him to Hopkins and acknowledging that no one in the country had better training in pharmacology. Besides having worked in Martin’s laboratory at Johns Hopkins, Abel was known to Welch and Osler and had corresponded with them during his travels in Europe (3, 6). He was thus happy to accept the Hopkins offer, including laboratory funds and professorial title, and establish the first chair explicitly and solely dedicated to pharmacology in the United States (6, 8). After a summer trip to Europe, Abel arrived in Baltimore in mid September, 1893, in time to greet the Johns Hopkins Medical School’s first class (3, 8). His family soon joined him, and Mary worked to improve city food standards through her appointment to the Baltimore board of supervisors of city charities (11).

Because the incoming medical students would not take his pharmacology course until their second year (in 1894), Abel offered physiological chemistry (then a subdiscipline under pharmacology) as his inauguration into teaching at Hopkins in 1893 (3). As at Michigan, the pharmacology course consisted of lectures (five per week), plus experimental demonstrations a combination that became a mainstay at Hopkins. Abel added a required laboratory component, in which students worked in groups of four and investigated the effects of various drugs on anesthetized laboratory animals (3, 6, 8, 11).

Early in his career, Abel spent countless hours preparing lectures and teaching, but medical students did not regard him as an especially good lecturer. Over time, he turned over much of his lecture hall responsibilities to his postdoctoral fellows (2, 3, 5, 13) but maintained an interest in the pharmacology laboratory course, which was very popular, despite suboptimal equipment. Abel made a point of engaging students during their experiments. After ten years, he made the laboratory course an elective, restricted to forty-five students. Competition was keen, and students would “buy” places into the class from each other (3, 14, 15).

Abel was an enormous influence as a pharmacology mentor (as opposed to lecturer) to a generation of postdoctoral fellows in his laboratory. During his first two decades at Hopkins, he provided one of the few laboratories, and certainly the most prominent one, where graduate students could study pharmacology in the United States (3, 6). To Abel, the ideal education for a pharmacologist was similar to his own, largely European, odyssey: a solid grounding in chemistry and physics followed by training in medicine, preferably including an MD degree. He opposed establishing a pharmacology PhD program, which was not instituted at Hopkins until 1969. Most of his proteges already had advanced degrees and were essentially postdoctoral fellows. They received their pharmacology training by conducting research in his laboratory and teaching pharmacology to the medical students (3, 6). Abel taught his proteges by example. His never-changing laboratory attire white surgical cap, gray sack coat, and long white apron embodied the idealized figure of a German professor (5, 7, 15). His work ethic was European, but his intense enthusiasm, youthful outlook, tremendous optimism, dogged determination, and most of all, his personal warmth were decidedly modern and American (2, 7, 13).

The Lunch Table Discussions

The main forum for scientific development in Abel’s laboratory was the daily brown bag lunch discussions, which replaced the formal seminars typical of most departments. A small room next to Abel’s laboratory, containing a work bench and a chemical hood, served as the lunch room. The legs of the oilcloth-covered lunch table were immersed in cans of kerosene to discourage Baltimore’s predatory cockroaches (5, 7, 14). Each day, the laboratory staff, along with invited Hopkins faculty members and visiting scientists, would bring their lunches, to be supplemented with tea and Abel’s favorite cookies, to the work room. Mary’s considerable culinary talents were also known at the table (3, 12, 16).

Surrounded by anesthetized dogs in the midst of an experiment, Abel led the group in an informal exchange of ideas and scientific problem solving, peppered with doses of suggestion, criticism, encouragement, and sometimes heated arguments (2, 8, 13, 15). Abel gave priority to the research activities of his staff, but the discussions also included inter- and intradepartmental affairs and his interests in mathematics, the arts, and sailing (6, 12). Despite his rank as department chairman, foremost pharmacologist in the country, and world-renowned scientist, Abel engaged all personnel in uninhibited discussion (15, 17). Leonard Rowntree, one of his postdoctoral fellows, commented (16), “If in my eight years at Hopkins, had I done nothing but attend the professor’s luncheons, I would have acquired a liberal education and learned, in addition, the secret of successful graduate teaching.” As his laboratory became known for training pharmacologists, professional colleagues increasingly consulted Abel when staffing pharmacologists at their institutions. A recommendation from Abel proved valuable to many of the future pharmacology directors who had sat around his laboratory luncheon table (3).

Abel’s Work Environment

For most of Abel’s tenure at Hopkins, his department had no secretary and shared a single telephone. His office was an open corner of his laboratory containing an old, roll-top desk, a canvas army cot, and a large table piled high with papers, books, and current periodicals. Despite the austerity, he was remarkably productive and attracted a steady stream of unsolicited trainees and coworkers (13, 15). Abel greeted new arrivals to his laboratory with a warm smile, throwing his arm around their shoulders, and for that moment making them the center of his universe (7, 15, 18). Everyone, including Abel, conducted his own laboratory experiments (13, 14).

Thoroughness, precision, and persistence characterized all his work. His experimental technique was elegant, whether measuring minute amounts of material or cleaning a pipette (7, 17). A workhorse who pushed himself to exhaustion, Abel catalyzed the research of everyone around him in a congenial, supportive manner. Laboratory experiments often ran well into the night and through weekends (2, 5, 8, 12, 13, 15). His eagerness to complete an experiment sometimes derailed his promises to Mary for a Sunday matinee or a holiday picnic. Equally often, however, he would invite those working late for supper and a show, and once a week he took his entire organization out to bowl (7, 8, 12, 13, 15, 16).

Physical infirmities did nothing to deter his devotion to the laboratory. In 1900, a laboratory explosion sprayed glass shards that destroyed one of his eyes. Although he never discussed the accident, most photos of Abel after that date are taken from his left side. In later years, he suffered increasingly from debilitating headaches, which only strengthened his resolve to work. In 1926, he was struck by a car on his way home from the laboratory, fracturing his leg. Although nearly 70, he was back at the bench in a few days, on crutches and in a cast, working with his accustomed zeal (7, 8, 15).

Establishing Journals and Societies

Despite Abel’s passion for the laboratory, his most lasting contributions were to organize professional societies and establish scientific journals (2). Abel was barely settled at Johns Hopkins when he floated the idea of an American journal to communicate progress in experimental pathology, pharmacology, and biochemistry. He persuaded President Gilman and the medical faculty to establish the Journal of Experimental Medicine, which first appeared in January, 1896, with Welch as editor-in-chief and Abel among the associate editors. Abel next engaged Christian Herter, professor of pharmacology at Columbia University, to help establish a journal specific to biochemistry. Despite concerns about a sufficient number of suitable papers, the first issue of the Journal of Biological Chemistry appeared, with Herter providing the financing, in October, 1905, under Abel and Herter as joint editors (8). On December 26 of the following year, Abel called biological chemists to New York City (4, 8) to organize and promote biochemistry as a research field and a separate preclinical discipline in medical school. The first meeting of the American Society of Biological Chemists took place in Washington, DC, in May, 1907. In keeping with his opinion that biochemistry was a separate discipline, Abel relinquished jurisdiction over physiological chemistry at Johns Hopkins in 1908. Walter Jones, who was one of Abel’s early associates, became its first departmental chairman (3, 8).

Finally, Abel targeted his own discipline. “It is high time that we started a society,” he wrote to Torald Sollmann in 1908, arguing that young pharmacologists should have a forum for presenting and discussing their research (6). On December 28, 1908, Abel met with seventeen scientists in a medical school lecture room at Hopkins to organize a national pharmacology society. The new society’s name required some thoughtful discussion, as a commercial group promoting the applied fields of pharmacy, pharmacognosy, pharma-codynamics, and therapeutics had already named itself the American Pharmacological Society. In addition, Abel and his colleagues recalled that Paul Ehrlich had emphasized, in addition to pharmacological responses in healthy animals, the need to test drugs on animals with experimentally induced diseases, a field he called experimental therapeutics (3). Abel and colleagues therefore settled on the American Society for Pharmacology and Experimental Therapeutics. Abel was elected president, and his proteges Reid Hunt and Arthur Loevenhart became secretary and treasurer, respectively. An executive council, consisting of the officers and four councilors, agreed to prepare the society’s governing constitution over the coming year (3). The founding of ASPET has been reviewed in detail by Chen and by Parascandola (19, 20).

The Journal of Pharmacology and Experimental Therapeutics (JPET)

Abel simultaneously moved forward with plans to establish an American pharmacology journal, with an eye on Waverly Press of the Williams & Wilkins Company, which was then printing the Journal of Biological Chemistry. Unable to attract the kind of funding that Herter had provided to start the Journal of Biological Chemistry, Abel proposed to Edward Passano, president of Williams & Wilkins, that the publishing house serve as both printer and publisher of the new journal. Abel, along with Hunt and Carl Voegtlin, established the Journal of Pharmacology and Experimental Therapeutics as an independent corporation, which they owned. On March 16, 1909, Abel and Passano signed the contract for the new journal, marking the beginning of Williams & Wilkins as a prolific publisher of scientific journals (3, 6).

The first issue of the JPET appeared in June, 1909, with Abel as editor-in-chief. Abel intended to publish six issues annually, and he broadly solicited pharmacology and experimental therapeutics papers. JPET’s first year of publication (1909–1910) consisted of one volume containing thirty-three papers, of which twenty-four came from academic institutions, six from government agencies, three from the private Rockefeller Institute, but none from industrial laboratories (3, 6). Mary paralleled her husband’s professional activities. In 1908, she was instrumental, along with Ellen Richards, in forming the American Home Economics Association, and in 1909, she became the first editor of the Journal of Home Economics (3, 11).

On December 29–30, 1909, the first annual ASPET meeting was held, in Boston, with a program consisting of fifteen papers and four demonstrations. At the business meeting, the executive council recognized a roster of thirty-four members, adopted the constitution, and elected officers. Abel continued to serve as president of ASPET until 1912, the same year he was elected to the National Academy of Sciences (2–4, 6, 19). In 1911, Arthur Cushny, who had succeeded Abel as chair at the University of Michigan and was now professor of pharmacology at University College, London, contacted Abel about expanding the scope of JPET to include British research. British pharmacologists did not have their own society or journal. Abel and the editorial board embraced Cushny’s proposal, because British papers would bolster JPET’s financial stability and the prestige of its contents. JPET continued to report American and British pharmacology research until the British Pharmacological Society established its own journal in 1946 (21).

In the first decade of JPET, Abel exercised little editorial oversight. Manuscripts submitted by established pharmacologists, editorial board members, and especially workers in his laboratory, were not refereed (3, 13, 15). Occasionally, he would ask Williams & Wilkins to hold the next issue of JPET so he could report on ongoing research (15, 22). By the 1920s, the length and number of papers created a backlog. Abel reluctantly engaged referees, but he still hesitated to offend established scientists. He disliked arbitrating disagreements and would sometimes reverse a referee’s rejection if the author pressed the point (3). However, Abel strictly enforced editorial policies concerning vivisection and advertising. Animal experimentation was fundamental to pharmacology research at the time, but as a journal editor, Abel was sensitive to animal activists’ sentiments, and he rejected papers involving surgery on unanesthetized animals (3). He also prohibited cigarette advertizing, explaining that he preferred advertisements from chemical firms, book publishers, and instrument makers. Pharmaceutical advertisements provided much-needed revenue, but he imposed strict limits on drug advertising copy and actually would have preferred none at all (3).

Whether in his laboratory or the armchair of his book-crammed study at home, Abel voraciously, critically and widely read the scientific literature in several languages, including German and Greek. His recreational reading, even on summer vacation in Randolph, New Hampshire, was anything but light: physics, astronomy, the history of medicine, and even Latin grammar (2, 7, 8, 15, 17). He also read the Encyclopedia Britannica relishing the mistakes he found and arrived early at the barber shop to read the latest issue of the National Police Gazette, the National Inquirer of its day [(15); George Koelle, personal memoir, 1994]. When he was invited to present a public lecture, Abel would spend months searching the literature for original sources, delving deeply into historical material, and checking references meticulously. He would lighten these lectures with stories that showcased his keen sense of humor (7, 13, 15).

Abel’s Research

After launching ASPET and the JPET, Abel devoted most of his energy to research. His modest laboratory drew scientists from all over the world. Working side by side with his coworkers, he tackled difficult questions with eternal optimism (8, 15). Over the course of five decades, Abel published ninety papers, showing his originality and breadth of knowledge. His laboratory accomplishments have been extensively reviewed by Voegtlin (8) and are summarized in Table 1⇓. Primarily a biochemical pharmacologist, Abel preferred to isolate biological substances (hormones and toxins) and study their mechanisms of action (7). Of his diverse investigations, four achievements stand out: epinephrine; a prototype artificial kidney; insulin crystallization; and the dual neuronal action of tetanus toxin.

Referencing published reports, Abel attempted to isolate the vasopressor substance present in adrenal medulla extracts. In 1897, he crystallized a substance from sheep adrenal glands and called it “epinephrin.” Although Abel’s substance induced a rise in blood pressure, he had actually crystallized the monobenzoyl derivative of epinephrine. Other investigators would subsequently isolate and identify two natural substances, epinephrine and norepinephrine, and Abel publicly, at least praised their work (3, 8). In 1913, Abel became interested in removing diffusible substances from blood by dialysis (a method he called “vividiffusion”), which he thought would be useful in renal failure. He built a working device and successfully used it to demonstrate for the first time the presence of free amino acids in normal blood (8).

In 1922, Banting and Best demonstrated the benefits of insulin in treating diabetes, but their pancreatic extract contained many impurities. Working in collaboration with Arthur Noyes, professor of physical chemistry at the California Institute of Technology, Abel spent four years isolating and purifying the hormone. His initial report describing insulin crystals was controversial, partly because he had difficulty reproducing his work and partly because conventional wisdom at the time refuted the notion that hormones were proteins. Eventually, by 1929, workers in independent laboratories confirmed Abel’s original work, which remains an important scientific contribution (3, 8).

Retirement

In 1932, at the age of seventy-five, Abel retired as the chair of pharmacology at Johns Hopkins and editor of JPET, handing over both responsibilities to E.K. Marshall, Jr., one of his proteges. Abel then served a term as president of the American Association for the Advancement of Science (2, 3, 21).

As editor and owner of JPET, Abel had always provided space for the abstracts of papers presented at ASPET meetings, but in fact ASPET had no official connection with JPET. In 1933, Abel initiated a series of discussions between ASPET’s executive council and Edward Passano, offering to transfer JPET from his corporation to the Society. ASPET wanted to assume ownership, but Passano, who still maintained a close personal friendship with Abel, pressed ASPET for terms that would protect the future financial interests of Williams & Wilkins. In a skillful display of shuttle diplomacy, Abel convinced Passano to withdraw his demands, and on October 19, 1933, the newly executed contract finally made the Journal of Pharmacology and Experimental Therapeutics the official organ of ASPET (21).

When Abel retired, Johns Hopkins created an autonomous Laboratory for Endocrine Research so that he could continue his research as a professor emeritus. Although he directed the endocrine laboratory, Abel devoted his remaining years entirely to investigations of tetanus toxin, a surprising departure from his earlier interests. Determined and meticulous as ever, he demonstrated that all of the symptoms of tetanus can be explained by a dual action of the toxin on the central and peripheral nervous systems, and that the toxin distributes systemically via the vascular and lymphatic systems (3, 5, 8).

Shortly before Abel’s retirement, Mary suffered the first of several strokes. She had always deferred her plans and engagements to her husband’s and enthusiastically cooperated with him. She read all of his writings critically, and they candidly discussed problems together. In addition, she had played a conspicuous role in the social life of Abel’s department and was a gracious hostess to his staff (3, 7, 12, 15). Her own illustrious career included her editorship of the Journal of Home Economics until 1915, and her textbook, Successful Family Life on the Moderate Income, was used for many years in college courses of home economics (7, 11).

In 1935, Mary became paralyzed on her left side and suffered some mental impairment. She subsequently required full-time nursing until her death, on January 20, 1938, at the age of eighty-seven (3). Despite this loss, Abel continued to work actively in his laboratory until the spring, when he developed a cough, which progressed to bronchopneumonia. Although he curtailed his activities, Abel resisted treatment for several weeks and only reluctantly entered Johns Hopkins Hospital (17). From his hospital bed, on May 26, 1938, Abel discussed plans for continuing his research on tetanus toxin with William Chalian, one of his associates. He also received notification of his election to the Royal Society of London, as a foreign member. A few hours later, John Jacob Abel died from a myocardial infarction, a week after his eighty-first birthday (8, 17).

Abel’s Legacy

Abel’s influence on pharmacology has been widespread and long-lasting. In his lifetime, numerous institutions and societies recognized his contributions with medals, honorary degrees, and honorary memberships (2, 8). Despite the increased use of computer simulations, laboratory rotations not too different from the ones Abel introduced at Michigan are still an integral part of pharmacology graduate training programs (23). Now, more than ever, pharmacology students explore the molecular actions of drugs, a perspective that Abel always championed. It is fitting, too, that ASPET’s John Jacob Abel Award recognizes the research of young pharmacologists. From a simple lunch table in Baltimore, generations of newly minted pharmacologists emerged and spread Abel’s philosophy, which now dominates the field.

In 2008, in conjunction with the centennial celebrations of ASPET’s founding, 7,800 society members demonstrated their connection to Abel through networks of coauthored publications. Organizers of the “Abel number” exercise estimate that nearly all ASPET members can claim Abel as an antecedent by tracing the coauthors of their coauthors [(24); David Bylund, personal communication). From a single volume of thirty-three papers in its first year of publication, JPET has also steadily grown. In its hundredth year (in 2008), JPET issued four volumes, containing 468 papers. The authors represented 341 academic and research laboratories, of which 223 were outside the United States, plus laboratories at twenty-six government agencies and seventy commercial organizations.

Abel’s place in pharmacology is secure. He was a shy and gentle man who nevertheless shaped a new scientific discipline; a poor lecturer who nevertheless trained a generation of influential pharmacologists; a passive arbiter who nevertheless founded and edited three prestigious scientific journals; and a passionate, tireless researcher who is remembered for his organizational and administrative accomplishments. And in recalling the declaration he had made to his young wife, back in 1890, when he wrote, “I know that I can make vastly more out of pharmacology in the States,” we must all agree, that he was indeed a man who kept his word.