Dr. Arthur Heffter

The Heffter Research Institute was named in honor of Dr. Arthur Heffter. Yet, even among those knowledgeable in the history of psychedelic and psychoactive substances, few can readily identify Dr. Heffter's seminal contribution to this field, which was the identification of mescaline as the active principle in the peyote cactus. Fewer still know anything at all about the man himself. In fact, Arthur Heffter was a leader during the classical period of Pharmacology, was the first chairman of the German Society of Pharmacologists, and was largely responsible for the first Handbook of Experimental Pharmacology. The following short description of his life and work will attempt to highlight some of Heffter's achievements.

Arthur Heffter was born in Leipzig on June 15, 1859, the only child of a well-known business family. His father died when Arthur was very young, forcing him to become rather independent at an early age. He received his lower education at the Leipzig Nikolagymnasium.

He then studied chemistry in Freiburg, Leipzig, and finally at Greifswald where in 1883 he received his Ph.D. under Limpricht with a dissertation entitled 'Some new sulfur compounds derived from p-toluidine.' In 1884 he briefly served as Assistant to the agricultural chemist Maercker at the Agricultural-Chemical Research Station in Halle, but soon left and from 1884-1886 assisted O. Nasse, a pharmacologist and physiological chemist, in Rostock, and worked on the excretion of sulfur in urine. He showed that the sulfur in food is converted to hydrogen sulfide in the intestines, which is absorbed and then oxidized to hyposulfurous acid. Most of the latter is further oxidized to sulfate, with a small amount appearing in the urine as thiosulfate. These studies strengthened Heffter's interest in pharmacology and he decided to study medicine at the Pharmacological Institute at Leipzig. During this period he worked in the laboratory of Rudolph Boehm, where he discovered choralose, a compound produced by combining chloral and glucose, that until recently was used extensively in pharmacology as an anesthetic agent for animal experiments.

Heffter received his M.D. degree and doctorate in pharmacology at Leipzig in 1890. He was appointed university lecturer in 1891, the year he was married, and worked for one semester in 1892 to learn the methods used in the laboratory of the renowned Oswald Schmiedeberg at Strasburg, which at that time was the most famous pharmacology laboratory in the world. He then returned to begin his official position at the Liepzig Institute to work again with his teacher Rudolph Boehm, where he set a brisk pace. In 1896 Heffter became a full professor at Leipzig.

Our decision to name a research institute in honor of Arthur Heffter was based largely on seminal work he began at about this time on alkaloids derived from the peyote cactus (Lophophora williamsii, which was then called Anhalonium williamsii). Earlier, in 1888, the famous Berlin toxicologist Louis Lewin had received dried samples of peyote 'buttons' from the Parke-Davis Pharmaceutical company and had been able to show that an alkaloid was present in the cactus. Heffter obtained samples of this cactus and was able to isolate several pure alkaloids from it and from the related cactus Anhalonium Lewinii. He isolated and char–acterized the pharmacological properties of the alkaloids anhalonine, pellotine, anhalonidine, lophophorine, and mescaline. In particular, using both animal experiments, and in self-experiments, he showed that mescaline was the alkaloid responsible for the profound psychoactive properties of peyote. Thus, Heffter was the first scientist to study system–atically a naturally-occurring psychedelic material. This classic study, published in 1897 has been characterized as among some of the best pharmacological work produced up to that time. That same year, Heffter was named an exceptional professor. Because of these experiments, mescaline was eventually synthesized by Ernst Späth in 1919, thus allowing studies of its clinical effects in the early part of this century. It would be nearly 50 years before the Swiss chemist Albert Hofmann would discover the effects of LSD and would begin studies that would, to a certain extent, parallel Heffter's.

During this period he had numerous other projects, which included the study of the lecithin content of the liver in normal individuals and in those who had been poisoned by phosphorus. He studied the lactic acid content of muscles following poisoning by various toxins such as strychnine, carbon monoxide, and curare. With one of his students (Anten) he worked out an excellent way to identify iodine in organs and in organic liquids. He also isolated a number of pure substances from South African fern root (Rhizoma pannae) including safrol and isosafrol and, in conjunction with Böhm's work on the German fern root demonstrated the relationship of the two plants. Rhizoma pannae was used at that time as an anthelmintic agent (to combat intestinal worms) and he showed that the metabolism of safrol and isosafrol played a major role in the effects of these compounds.

In 1898 Heffter left Leipzig to take over as Chairman of the physiological-pharmacological branch of the State Health Office. This appointment may have awakened in him an interest in industrial hygiene, but later the same year he moved to the University of Bern as Professor of Medical Chemistry and Pharmacology. He characterized these 'Swiss years' as the happiest time of his life. He had fresh energy, and found himself at a well-equipped institute in a beautiful environment with numerous interested students and like-minded colleagues. This time proved productive for him, and his family life also brought him much joy.

He had married in 1891 and had three daughters; two more were born while he was in Bern. Although he continued his studies on cactus alkaloids, his interests changed in Bern, partly due to the stimulating influence of the dermatologist Jadassohn. He became interested in the excretion of frequently used medicines, and their transformations by various organisms. This interest led to studies on the fate of arsenic and cacodylic acid, the absorption, distribution, and excretion of iodine, and the excretion of lithium, mercury, and quinine. He first recognized the deposition of arsenic in hair, which led to the well known forensic test for arsenic poisoning by hair analysis. During this period he demonstrated that isolated animal tissues could convert sulfur into hydrogen sulfide, which he had already shown occurred in the intact animal, thus demonstrating that this process was a specific chemical reaction, and not the product of fermentation. He showed that the tissue could reduce not only sulfur, but also cacodylic acid and mercuric chloride, and characterized the reducing agent as cysteine. Heffter thus explained not only the laxative action of elemental sulfur, but recognized the important and fundamental role of the sulfhydryl group in these reductions.

In 1906 it was with great difficulty and sadness that he moved to the University of Marburg to accept the Chair. He did this to prevent the chair there from being demoted (or downgraded) to 'extra-ordinary.' While at Marburg he continued his research and demonstrated that an extract of lung tissue could reduce both nitrate and nitrobenzene, also showing that fermentation mechanisms were not responsible. Two years later, in 1908, he moved to Berlin to fill Liebreich's Chair, where he would spend the next 16 years in the top position of the German empire.

His task at Berlin was to modernize the Institute and change the direction of study. He created a department for immunization research and experimental therapies. For nine years he colla­borated with Friedberger. There, with his student Fritz Sachs, he described a crystalline glycoside from strophanthus kombe. While at Berlin he continued work with arsenic, the analysis and evaluation of digitalis-Korper, the pharmacology of camphor, the identification of benzene in organs, the reasons for the resistance of rabbits to atropine, and many other projects. He was elected Dean of the Medical Faculty in 1915.

In view of his widely-recognized expertise, Heffter was called on at about this time to make contributions to various handbooks, particularly those on toxicology, and he also worked on collected reports for Virchow's Yearbook. In collaboration with Ewald, he completed a handbook on the categorization of medicines. He next formulated a plan for a handbook on experimental pharmacology. Unfortunately, this latter project was delayed because of World War I and the hard times following the war. Ultimately, the Handbook of Experimental Pharmacology was published, although Heffter did not live to see its publication. Written with many colleagues, this work was the first attempt to summarize everything that was known in the young science of pharmacology up to that time and was a critical milestone in defining the science of pharma­cology.

Following this period of writing, Heffter returned to the laboratory, studying preparations of strophanthin, the durability and determination of the potency of digitalis leaves, experiments on synthetic camphor, and poisoning by benzene, tetrachloroethane, and other substances. He pursued the study of shepherdÕs purse as a substitute for ergot.

Heffter's expertise was extensive, particularly in the area of poisoning, and in all questions of the processing of medicine, food hygiene, and industrial hygiene. His judgment was always carefully based and therefore completely trustworthy and convincing. He was greatly concerned about public health, and also addressed practical issues of the time such as the admissible levels of lead in beer lids, the toxicity of airplane wing paint, and the addition of formic acid to lemonade. In each situation he knew not only the final expert word, but also set a standard and made interesting pharmacological finds in the process. Upon his death he was a member of the work committee of the German Society for Industrial Hygiene.

In his later years at Berlin it became clear that Heffter was seriously ill with cerebral arteriosclerosis. His appointment as Rector of the University of Berlin in 1922 took the last of his strength and in the beginning of the 1924-25 winter semester, Heffter's medical condition quickly worsened, and he died on February 8, 1925.

At the University of Berlin in 1923 with his assistants

At the time when Heffter lived, it was unusual for scientists to have training both in chemistry and in medicine. Although today it appears as an obvious bridge, it was not as clear at that time that training in chemistry could provide a useful background for the study of medicine. It was his training in these two subjects that provided the tools for many of Heffter's studies of metabolism, pharmacology, and physiology. He quite clearly had an interdisciplinary perspective on his research that today is recognized as the most powerful approach to the solution of biomedical problems.

Regarding his personal character, Arthur Heffter was quite a remarkable man. To provide some historical perspective, it may be worth pointing out that in the European university system, there is generally only one person in an entire laboratory or department that holds a position equivalent to 'full professor.' These positions are rare and highly sought after because they typically become available only upon the death or retirement of a professor. They are generally awarded to the best and the brightest. It was quite common, particularly in years past, that all work published from a laboratory carried the name of the professor as one of the co-authors, whether or not he made any real contribution to the project. Against this background, what was Arthur Heffter like? One of his former students commented, on the occasion of what would have been Heffter's 100th birthday, "It is impossible to find out everything that Heffter found due to the indices of the relevant literature. Many of his ideas and experimental results were included in works of his students, where his name was not even mentioned. He did not insist on being quoted because of his modesty; in many cases he directly forbade it." This was a quite remarkable characteristic, particularly for a German scientist at the turn of the century!

Heffter's personality had a powerful charm. He did not throw his weight around to impress others, although as we can see from the range of his achievements he was an extremely well respected authority on many fronts. He was supportive to his students, assistants, and colleagues without expecting anything in return; it would have been against his nature, which was very reserved. He was a noble thinker, and a good man. He led his institute with finesse and admirable calmness.

Although he did not have a large circle of close friends, those that were close to him found him enduring and warm. Heffter had a sense for everything that made life beautiful and worth living. He had a particular love for music and added the following to his doctoral dissertation, "Robert Schumann as theoretical and practical musician was eminently influenced by Johann Sebastian Bach."

We believe it is a fitting tribute that our Institute is named after Arthur Heffter. Not only was he the first scientist to study a psychedelic substance in a systematic way, but he was a brilliant and productive researcher and a warm human being loved by his colleagues.