Pharmacology education for medical students

Pharmacology is the study of the effect of drugs on the body. Instruction was preclinical – from the lectern. But not only medical students followed the lectures. Future pharmacists were able to participate in university studies and were examined by university professors, even though they were not officially students at the time. The course material consisted of drugs – raw materials from flora and fauna used to manufacture medicines. The drugs were an important part of both the curriculum and the exams.

For his classes, Holst had to borrow medicinal plants from the city’s pharmacies. Since this was quite cumbersome, he began to build up his own collection of drugs. At the university’s 50th anniversary in 1851, Holst looked back on those days:

When I entered into my position at the university in 1824, there was no pharmacological collection. Professor Sørensen [sic], who for 9 years before me had lectured on pharmacology, had to borrow specimens from the state pharmacies for each of his lectures, mostly from the Elephant [Pharmacy]. Thus, when the medical faculty upon my appointment decided that I should take over the lectures on pharmacology, I proposed to the Academic Council in a letter of 26 May 1824 that of the university’s funds the sum of 300 speciedaler be allotted to t he acquisition of such a collection with containers and cabinets for safe-keeping.*Fremstilling af det pharmakologiske Museums Tilbliven og Udvikling (Meddelt af Prof. Dr. Holst, den 30te April 1861), in Det Kongelige Norske Frederiks Universitets Aarsberetning 1861 (Annual Report of the Royal Frederick University, 1861), pp. 93–95.

It is difficult to get a clear impression of the size of the collection at the time Holst was granted these funds for the purchase of drugs, repositories and storage cabinets. His descriptions of the basic financial conditions make it clear, however, that the new university had modest means.

The drug collection was placed in Anatomikammergården, also known as Anatomigården, House of Anatomy. The small building, Oslo’s oldest half-timbered house, is located at Rådhusgaten 19 and was rented by the university for medical training, including lectures and dissections. It also housed the surgical instrument collection and a collection of anatomical specimens.

The pharmacological drug collection was installed in the medical faculty’s staff and assembly room, which furthermore served as a study for the prosector and lecturer in anatomy. Additionally, it functioned as the faculty meeting room, dressing room and joint office. All of these various functions did not exactly facilitate an expansion of the collection, which therefore consisted only of drugs that were essential to lectures and exams. The drugs had been selected with a particular view to the current Pharmacopoeia Danica from 1805,*harmacopoea Danica, Regia autoritate a Collegio sanitatis regio medico-chirurgico Hafniensi conscripta. Hafnia, Brummer, 1805. the official overview of the drugs pharmacists were required to keep in stock and their specifications.

In 1834, ten years after Holst became a professor, the collection had grown to 649 samples. That year, only ten samples were added, showing that the material grew on a sporadic basis. By then it had become obvious that a lot of work was required to maintain the collection, since Holst wrote in the university’s annual report that “a great deal has to be discarded as it is spoilt and unusable.”*Annual Report of the Royal Frederick University, 1833–1834. So many spoilt drugs had to be thrown away that the collection had actually decreased by 30 specimens in 1840. That year, 32 chemical plant and animal samples were added. “By the end of the year, the collection consisted of 28 samples from the animal kingdom, 463 from the plant kingdom, and 189 from the mineral kingdom, totalling 680 samples.”*Annual Report of the Royal Frederick University, 1840.

Some years, the collection did not grow. In 1845, pharmacist Møller contributed 38 samples – roots and bark from exotic plants, including various Chinese types of bark that had recently been taken into use by the medical profession.*Annual Report of the Royal Frederick University, 1845.

After two decades, the drug collection had begun to suffer from age. A firm, concluding sentence in the annual report about the collection reads: “Over the years, a great deal of spoilt specimens have furthermore been discarded and replaced with fresh and healthy samples.” Being in charge of a major drug collection may have felt like a Sisyphean task.

When the monumental university complex on Karl Johans gate, Oslo’s main thoroughfare, was completed in 1852, conditions improved considerably. In the introduction to his catalogue, Holst writes that “thus, the collection may be divided into two periods, one from 1824 to 1851, the other from 1852 to the present, an important observation because its development has been quite different in each period.”

At the time, the central building was called Museum Naturale and was to house the museums of natural history, as well as physics, chemistry and medicine. The latter was located in the east wing of the building together with zoological and zootomical collections. The connection between medicine and zoology had been a deliberate choice in the planning process. Christian Boeck (1798–1877), a physician who was also in charge of veterinary medicine, was the only university professor on the building commission. Comparative anatomy was to be the connecting link between medical studies and natural science. Medical students were to study the anatomy of both humans and animals.

The pharmacological collection was allocated a small room between two auditoriums on the 2nd floor, namely Auditorium 15 for medical lectures and Auditorium 14 for zoology. The architectural drawings show that it was to house the collection and function as an exam room. In practice, it was also used as an office for the senior lecturer. Nonetheless, conditions improved significantly for the collection.

The drugs were used in lectures and group instruction. The new premises furthermore allowed Holst to offer students and other interested parties access to the drug collections for self-study, subject to agreement.*From 1856 on, the study catalogue listed the drug collection together with the other publicly available university collections. Holst writes that he wanted to establish regular opening hours, just like the other educational collections and university museums. For practical reasons, however, this was not possible, even though the premises had been improved. All the same, Holst admitted that there had not been many requests to visit the collection: “(…) since the general public hardly has particular interest in viewing a collection of pharmaceutical raw materials and specimens used as medicaments.”

The new university complex made it possible for Holst to expand, and many new drugs were added during the following decade. During the same year he moved into the new premises, the collection increased by 200 samples. Holst’s accounts for the university’s annual report tell us that starting in 1855 he travelled abroad during the summer holidays and traded in or received drug samples from chemical factories, pharmacies, and pharmacological museums. In the anniversary report of 1861, Holst describes the rapid growth of the collection:

The largest part of the collection has been acquired through purchase from allocated funds; but several hundred specimina, thereamong some rather valuable ones, have been donated by pharmacists here in the city, as well as chemists and chemical factories abroad, with whom I have established relations on my annual travels when the university had summer holidays. Particular mention among the museum’s more significant donors must be given to chemists Gehe & Co. in Dresden, Hauffman & Lampe in Berlin, Professor Th. Martius in Erlangen, and the French Colonial Ministry, which recently despatched a considerable collection of plant-derived drugs from the French Colonies. The Dutch Colonial Ministry has promised a similar gift from the Dutch Colonies.*Fremstilling af det pharmakologiske Museums Tilbliven og Udvikling (Meddelt af Prof. Dr. Holst, den 30te April 1861), in Annual Report of the Royal Frederick University, 1861, pp. 93–95.

Not only the storage conditions had changed. In his catalogue, Holst points out that the field of pharmacognosy was rapidly evolving. This had led to an increase in the number of drugs in pharmacological collections elsewhere as well. Beginning in 1856, Norway had its first own official listing of medicinal drugs – Pharmacopoea Norvegica. A pharmacopoeiais an officially authorized book describing the drugs that are in regular use in the country. Chemical substances, drugs or preparations described in the pharmacopoeiawere to be stocked by all pharmacies and be identical in composition throughout a given country. The particular drug requirements and the number of officinal drugs varied from country to country. The pharmacopoeiaspecifies the quality requirements for the drugs and specifies methods to analyse them. Therefore, it was important to develop a Norwegian pharmacopoeiaas a replacement for the Danish one from 1805.

Holst was part of the committee that compiled the new Norwegian pharmacopoeia. He does not mention this project as the reason for acquiring new drugs, but it would seem likely that the new pharmacopoeiainfluenced the curriculum.

The large amount of new drugs quickly led to space problems, and several cabinets were installed in the adjacent auditorium. A few years later, these cabinets, too, were jam-packed.

While Holst was preparing his catalogue, a university committee reviewed the storage needs for all of the university’s collections. Holst was not particularly confident that conditions would improve in the near future.

Pharmacology was a major subject for medical students at the time. In Holst’s day, the subject was not taught according to a particular curriculum, and the lecture catalogue tells us that students were not necessarily taught the same from one year to another. In 1850 and 1851, Holst lectured on “the pharmacology of salts, fluids, and unweighable substances”. In 1852, it was “the toxicology of metals, followed by general pharmacology”. Eventually, Holst’s lecture plans became more detailed. He was teaching six days a week, and in 1853 his schedule was as follows: “Monday, Wednesday and Friday, lecturing on hygiene; Tuesday and Thursday, pharmacology; Saturday, preparing examinations on selected parts of pharmacology and toxicology.”

In the years that followed, we see different variations of this teaching schedule. Most of Holst’s time was dedicated to general pharmacology. Alternately, he also lectured on toxicology and hygiene, less frequently on the pharmacology of “metals and fluids”. On Saturdays he often arranged presentations and inspections of the drug collection. Thus, we can see that the drug collection was an integral and comprehensive part of the curriculum. And it was not only medical students who benefited from it.

Pharmaceutical apprentices

Pharmacists were not mentioned in the university statutes of 1824. Throughout the 19th century, scholars debated how much theoretical knowledge ought to be required of a pharmacist. If academic requirements became too strict, many feared it would be difficult to find apprentices for pharmacies. In 1836, a new law on pharmaceutical exams was passed. After an apprenticeship and practical training in a pharmacy, it now became common to sit in on university classes for some of the training period.

The future pharmacists attended lectures in natural history, physics, chemistry and pharmacology. This was followed by an exam, prepared by the professors in the relevant subjects and a pharmacist. The exams commenced with a six-hour test on “a subject of pharmacology that would not be expected to be unfamiliar to those who submit themselves to a pharmaceutical examination, nor could be answered directly on the basis of a book committed to memory.” Next was a practical exam consisting of three assignments – two analytical and one synthetic. The exam was held in the university’s chemical laboratory and stretched over the course of one or two days. Then the candidates underwent an oral exam with the exam committee: the natural history instructor examined zoology, botany and mineralogy; the physics or chemistry instructor examined physics and chemistry; the pharmacology instructor examined pharmacognosy, reading of prescriptions, and “the national legal provisionswith regard to powerful drugs”; the pharmacist examined pharmaceutics, knowledge of pharmaceutical goods and trade, and the assessment of prescriptions. All this took place in the course of two morning and two afternoon sessions.

Instruction and exams took place at the university but were not formally part of the curriculum. This hybrid solution is a good example of the interaction that has always existed between universities and society. Not until 1931 did pharmacy students formally qualify for enrolment at the university.

In 1855, the advisory medical committee proposed to establish a separate teaching position in pharmacy. The university’s professors of medicine were quite negative about the proposal. Frederik Holst, Christen Heiberg (1799–1872), Christian Boeck and Wilhelm Boeck (1808–1875) believed that a new teaching post was not advisable. Although it would serve to boost the field of pharmacy, in their experience the knowledge gaps among pharmaceutical candidates were not related to a lack of pharmaceutical expertise. Wilhelm Boeck argued that the problem was their poor education, not the training itself. The proposal was rejected.

At the same time, a proposal from the pharmaceutical exam commission was also up for debate. The commission wanted to raise the level of prerequisite knowledge among the pharmacy candidates. The candidates had worked as apprentices at a pharmacy before they came to university, and there was little control over what the pharmacist had taught them.

Discussions about the admission requirements and curriculum for the study of pharmaceutics came and went throughout the second half of the 19th century. Demands for more prerequisite knowledge were first voiced and rejected in the 1850s, then again in the 1890s. In the 1850s, the examination commission suggested that greater priority be given to quality assure of the apprenticeship in pharmacies, but the proposal was not adopted. Pharmacist Møller suggested that the relationship between pharmacist and disciple “must be just as private as that between a craftsman or merchant and his apprentice.”

There was widespread concern that stricter requirements for a basic education would lead to a lack of candidates in the profession. Public discussion was divided between two different views of pharmacy apprentices. On the one extreme, he was seen as a capable student on his way into a profession that required expertise. At the opposite end of the scale, the pharmacy apprentice was seen as a poor wretch who from childhood on had learned what it takes through practical work in pharmacies.

From collection to museum

As the theoretical basis of medicine rapidly changed throughout the 19th century, so did the hierarchical division of plants and drugs. Therefore, the teaching collection demanded continuous revision, a task Holst himself carried out during the forty-one years it was in his care. When Holst retired in 1865, it had grown into a large scientific collection consisting of 3237 different samples, and was named Museum pharmacologicum.

Before retiring, Holst catalogued the entire collection in meticulous handwriting. In his Catalogus Musei pharmacologici he divided the drugs and other specimens into 18 categories. Thus, the collection had started as a purely educational tool in order to avoid the extra work of borrowing samples from the pharmacy for every teaching session. In the course of Holst’s time as a professor, the collection was further developed and redefined as a research collection, and finally a museum.

The larger the collection grew, the more difficult it became to use in regular medical teaching. Besides, drugs were – and are – perishable. Since the 1820s, there had been many rounds of replacing “spoilt and unusable” drugs, but the oldest collection showed clear signs of age nonetheless. Holst’s successor, Professor Ernst Ferdinand Lochmann (1820–1891), saw the need for a smaller collection adapted to the needs of the students, and Holst’s collection was no longer actively used.

For several years, Holst had visited pharmacological museums throughout Europe, and in 1861, the same year he recorded its history for the university’s 50th anniversary, began to designate the collection as a “museum”. The name change also implied a raise in status, but Lochmann did not maintain the museum label.

Recreating the collection

Parts of the drug collection were found at the Department of Pharmacy, others at the Faculty of Medicine, specifically the Department of Pharmacology. The collection may have been split up when the subject of pharmacy finally got its own institute in 1931 with a new, beautiful building at Blindern. Perhaps parts of the collection were retrieved from the medical school in the centre of Oslo to be used for pharmacognosy classes in the start-up phase?

The Department of Pharmacy quickly built up a new collection of drugs. Today, the collection is located in the so-called “drug room” on the 2nd floor. At one point, Holst’s drugs were stored away, only to be recovered many years later in different parts of the basement. Some were kept in cabinets belonging to the Department of Pharmacognosy, others in cabinets of the Department of Galenic Pharmacy.

At the Department of Pharmacology, Institute of Clinical Medicine at Gaustad, Heidi Tømmerdal had ensured that old collections and other historical artifacts be taken along from Blindern when they moved in. In the late 1960s, the pharmacology department moved from the city centre to the building for preclinical odontology at Blindern. As of today, we do not know whether the collections were used for teaching at Blindern. At Gaustad they had been displayed in glass cabinets to decorate the corridors.* Today Georg Morgenstiernes hus.

Sometimes it only takes a few “gatekeepers” to save historical values. The fact that the catalogue, too, was preserved, promptly increased the value of the collection.

The different parts of the drug collection were assembled and registered by MUV and Smestad Paulsen. Then, Smestad Paulsen compared the drug labels with the information in Holst’s catalogue. Here, Holst had noted why he put together the collection, where the different samples came from, and from whom. He also described how he had employed the drug classification system in use at the time. The labels he had placed in each case included information about the plant taxonomy of most of the drugs.

In the 19th century, drugs were classified according to other principles than today. Since less was known about the various constituents and pharmacological properties, the systematization was based on concepts related to taste and physical properties.

Holst divided the 3237 samples into 18 different groups. The groups varied greatly in size, and they are distributed as shown in Table 1.

Table 1 shows the 3237 numbered items in the catalogue. Actually there were many more, because many items consisted of several specimens (anywhere from two to four). Therefore, the number of samples Holst registered is greater than the number of the last registered item specified in the catalogue.

At the end of the catalogue, Holst registered 38 samples that are neither classified nor numbered. He recorded the information included with the plants upon their receipt, and writes that they were not registered with the rest of the collection because he was sceptical about the information, whose quality he had not yet been able to assure. The catalogue also has a register that makes it easy to find drugs of particular interest.

In addition to the drugs at the Faculty of Medicine, Holst’s catalogue listed other chemical substances and preparations employed in the manufacture of medicines. The drugs belong to the first ten groups, up to and including number 2318. Following this, Holst registered various chemicals used in teaching and research. This included alcoholic fluids, acids, alkaline solutions, and salts in addition to a group called terra, or soil products, metals, and not least soaps and mud bath products. In the 19th century, the latter two were often used in a medical context. Baths were common in a number of treatment institutions throughout Europe, where, among other therapy options, the body was covered with mud. The Museum pharmacologicum covered everything a pharmacopoeia could be expected to cover, and much more.

Specimens used in the practical exam for pharmacy students

Professor Frederik Holst taught both medical and pharmaceutical students in the subject of pharmacology, and the collection was important for demonstrative purposes. Several of the drugs and chemicals in the collection were used in the practical exams for pharmacy students. Table 2 shows the collection items used in the practical exam for pharmaceutical students between 1856 and 1868. Each entry is numbered with reference to Holst’s catalogue and includes the name of the pharmacist who acted as examiner. There are no records of the particular tests the students were to take. The first Norwegian pharmacopoeia, which only lacks two items from the collection (nos. 2536 and 3169), was published in 1854.

However, the overview of drugs and other specimens that were used provides little information about how the exam for pharmacy students was conducted. What we know from other sources is that the future pharmacists went through several days of practical exams, and that they were expected to have a solid understanding of all products used in the manufacture of medicines, and all products sold at pharmacies.

Quantitative information for some of the samples in Holst’s catalogue

Holst’s catalogue lists several of the imported specimens by weight. These weight amounts are handwritten, like the rest of the catalogue, and have not been easy to decipher.* Schwarz 1963. For the contents of Table 3, please refer to the digitized version of the catalogue made available by the University Library in Oslo.* Search Oria or other search portals of the Oslo University Library for “Catalogus Musei pharmacologici Universitatis Regiæ Fredericianæ”. Berit Smestad Paulsen has managed to decipher many, but not all of the symbols for weight, an undertaking that may be continued by others. Some of the interpretations arrived at to date may be erroneous, and several of the specified quantities were not possible to interpret. The weight units in Table 4 are taken from Pharmacopoea Norvegica, 1854.

The issue of different standards of weights and measures has been an extremely important one in the history of science, not least in medicine and pharmacology. For example, in order to assess the effect of a given medicine on a patient, one must know the exact amounts used. Comparisons over time, such as by means of hospital records which in Denmark-Norway date back to the mid-18th century, depended on knowledge of specified amounts, as did international comparisons and the use of medical literature. Thus, it is problematic to transpose the measurement units of the time to the ones we use today. The weight unit pounds, for example, varied from one country to the next, as did ounces.

The source country of Holst’s catalogued samples is not always specified, but the labelled weight referred to the source country’s weight standard. In the European countries, the weight of one pound ranged from 350 g to 500 g. This can clearly be seen in the list from Pharmacopoea Norvegica, 1854 (Table 3).

Surviving drug samples from Holst’s collection

Holst’s catalogue is of particular interest because a number of drugs from the Museum pharmacologicum still exist. Three hundred and three drugs survive in small rectangular glass cases, while 114 more sizeable drugs are stored in other containers.

This book includes a full transcription of Holst’s overview of the Museum pharmacologicum,* Holst F. “Catalogus Musei pharmacologici Universitatis Regiæ Friedericianæ – Tables”. Michael 2021; 18; Supplement 27, pp. 75–205. as well as an overview of the drugs still in existence.* Paulsen, B.S., “Universitetets eldste drogesamling i 2021”. Michael 2021; 18: Supplement 27, pp. 206–17. The overview is particularly interesting because the labels inside the containers provide more information about the medicinal plants than the catalogue.

In addition to the names of the drugs, the catalogue lists their botanical classification. This 19th-century classification system largely uses the nomenclature adopted by Carl von Linné (1707–1778). Holst’s classification can be found in professor William Withering’s late 18th-century work on botany, A systematic arrangement of British plants. Professor William Withering (1741–1799) was a member of the Linnéan Society of London.* We have used the 4th edition, published by Withering’s son in 1801 (Withering 1801). Professor William Withering was a physician, botanist, geologist and chemist, and made the discovery that Digitalis purpurea, foxglove, could be used to treat dropsy. This is the origin of its use as a heart medicine. Schroff’s 1853 textbook on pharmacognosy was another important source.* Schroff 1853. Along with the information about plant classification, the catalogue frequently indicates where the plant material came from and who donated it.

It is important to note that many of the Latin plant and drug names used in Holst’s catalogue are no longer valid today. This also applies to numerous plant families. Therefore, the catalogue cannot be used as a modern reference work.

Where did all the drugs come from?

In the introduction to his catalogue, Holst describes how he acquired the various drugs. Between 1863 and 1865 he also gave several lectures at the Norwegian Medical Society on some of the drugs he had received for his collection. In these lectures, he described the specimens he had been given, where they came from, what they were used for, and in some cases he compared them with other drugs familiar to him* Holst in Norsk Mag Lægevidensk, 1863–1866..

Holst had an extensive network of professionals who furnished him with drugs. They included colleagues and pharmacists in several countries, drug suppliers and manufacturers who produced some of the pure drugs he obtained. He also had contact with the French Ministry of Algerian Affairs and other French colonies.

Holst’s collection is impressive. The drugs came from far away, including Latin America and the West Indies, particularly from the island of Réunion, from Brazil and India. All of this is described in Holst’s introduction to the catalogue, which holds a myriad of fascinating information for further study* Holst F. “Catalogus Musei pharmacologici Universitatis Regiæ Friedericianæ – Frederik Holsts egen innledning” (Frederik Holst’s own introduction). Michael 2021; 18: Supplement 27, pp. 51–74..

English translation: Thilo Reinhard

Web

World Flora Online: http://worldfloraonline.org/

The Plant List: http://www.theplantlist.org/