Historic background

In the 1970s, most new drugs were identified by screening new drug candidates in experimental animal models. In the 1980s, this screening was increasingly carried out with various in vitro assays which were able to identify the desired effect. In the 1990s, molecular pharmacology had almost entirely replaced screening in experimental animal models. In educational institutions, the focus in the biological sciences was on molecular biology and molecular pharmacology.

Achievements in these areas revealed very interesting perspectives both for elite university research into the development of new drugs and for the industrial development of new drugs. However, the need to put molecular observations in the context of the animal as a whole was overlooked. There are now very few researchers who have mastered this area, which is known as in vivo pharmacology. This shortage is a problem both in Denmark and internationally.

As early as the mid-1990s, the increasing international shortage of in vivo pharmacologists was featured in the journal The Lancet. In 1996, the huge shortage of in vivo pharmacologists in Denmark was on the agenda at a meeting of the Danish Society for Pharmacology and Toxicology.

The need for the industry and the universities to work together to train more in vivo pharmacologists was highlighted. Since then, the pharmaceutical industry has taken somewhat sporadic initiatives to co-finance a number of PhD students who have been trained as in vivo pharmacologists. In addition, the pharmaceutical industry has employed tens of foreign researchers with this background.

Shortage in qualified In vivo Pharmacologist

As a result of this significant exodus to the pharmaceutical industry, it has been impossible for the universities and higher educational establishments to retain researchers with a background in in vivo pharmacology, which in turn has caused difficulties for continuing education in this specialist area. In vivo pharmacology, which can be characterised somewhat simplistically as pharmacology in laboratory animals, requires access to facilities for experimental animals and laboratories where experimental work in animals can be carried out. Such facilities are expensive to set up, maintain and run. In addition, the costs of laboratory animals and their accommodation are considerable, while molecular pharmacology requires substantially fewer resources.

The backdrop to this research school is therefore a major shortage of in vivo pharmacologists, both in the drug industry and in terms of recruitment by the universities. It is crucial for continued development that such training gets under way, and on a scale that reflects the huge demand.

Head of Graduate Programme
Professor Jens Lykkesfeldt, Department of Veterinary and Animal Sciences, KU-SUND

Academic secretary
Helle Vinberg, Department of Veterinary and Animal Sciences, KU-SUND

Advisory board
Assoc. Prof. Anne-Marie Heegaard, Department of Drug Design & Pharmacology, KU-SUND

Assoc. Prof. Pernille Tveden-Nyborg, Department of Veterinary and Animal Sciences, KU-SUND

Senior Alliance Director, Innovation Outreach, Dorthe Lundsgaard, Novo Nordisk

Associate Director Michael Didriksen, PhD, Lundbeck A/S

Head of In Vivo Cell Efficacy and Histology, Jane Koch, Novo Nordisk

PhD stud. Penille Jensen, KU-SUND

PhD stud. Mads Jacob Bagi Nordsten, KU-SUND

The objectives of the graduate programme are

• to improve cooperation between universities and the pharmaceutical industry and establish a more formal and extended cooperation between research groups and supervisory environments in Danish universities involved in in vivo pharmacology,
• to help ensure that the research environments and competences of the pharmaceutical industry are used to provide perspectives on and inspire innovation in individual PhD projects as well as for the specialist areas involved,
• to help ensure that the PhD students have the opportunity to regard their own research effort as an integral part of the innovation in pharmaceutical research, from the initial concept to the final product,
• to function as a network for the PhD students to make it easier for them to establish contact with experts inside and outside their own research environment.

The Fall and Rise of In Vivo Pharmacology

In Vivo Pharmacology Training Group. British Pharmacological Society, 16 Angel Gate, City Road, London, UK EC1V 2SG.

Trends Pharmacol Sci. 23, 13-8, 2002.

Pharmacology is, by definition, the study of the mechanism of action of drugs, and requires a knowledge and understanding of responses to drugs induced both in vitro and in vivo. Such analysis of drug action is needed to transform molecular or cellular discoveries into clinical practice and, equally, to identify the molecular questions that arise from clinical observations. These studies are essential because responses observed in vitro can be magnified, diminished or totally different in the more complex integrated system. However, there is currently a severe shortage of pharmacologists with the skills needed to carry out in vivo studies in medical research, and a diminishing number of academic staff qualified to teach these skills to students. This article explores the reasons for this situation and outlines why in vivo work is vital for the analysis of drug action and for the discovery and development of new therapeutic agents.

In vivo we trust (Nature Reviews, Drug Discovery 2, 501–501, 2003) by Simon Frantz, Associate Editor (News), Nature Reviews Drug Discovery.

The pharmaceutical industry desperately needs the traditional skills of the pharmacologist

During the past two decades, in vivo pharmacology suffered a downturn of interest in both industry and graduate recruitment. Once the molecular biology revolution convinced us that it would solve all of our problems, academics feared that their papers would not be published if they did not contain a whiff of molecular biology, and they amended courses to ensure that their students would be properly prepared for the brave new world. Students were attracted by the glamour of molecular biology, preferring to isolate a gene involved in cancer than to isolate the ileum of a guinea-pig. This, and increasing pressure from animal-rights movements, persuaded many universities that the financial and ethical costs of running large animal houses was not justified.

In the intervening years, molecular biology has indeed had a marked effect on drug discovery. With the availability of the human genome sequence data, an incredible number of potential targets for small-molecule drugs are being identified. However, in the enthusiasm to jump on the genomics bandwagon, unfashionable areas in the pharmaceutical industry such as in vivo pharmacology suffered as a result of their second-class status.

But, more than ever, the pharmaceutical industry is realizing that no matter what the origin of the compound you are testing, or how it came into being, a good description of its pharmacological properties is necessary to assess its drug-like potential. There have been major advances in the use of cell culture and recombinant human cells, and in silico approaches are also providing valuable alternatives to animal experiments by simulating drug interaction and response data. But, these studies still cannot predict the integrated response of a potential drug as accurately as living systems, in which a combination of genetic, biochemical, physiological, pathological and environmental influences work in concert. With regulatory bodies demanding more and more information about drug safety, companies need reliable data from animal studies on the therapeutic potential of compounds.

So, the technologies that threatened to make in vivo pharmacology extinct have, in fact, re-emphasized its importance in drug discovery. And while the industry needs in vivo pharmacologists more than ever to assess the targets being generated, the decreased number of students with the appropriate skills emerging from the academic system is a big worry. This is a particular problem in the United States, which faces a major skills shortage because of the low recruitment of pharmacologists by universities 10–20 years ago. The lack of experience in the area is, in some cases, causing recruiters to stretch the definition of in vivo pharmacologists to anyone who can find their way around a rat.

To address these issues, pharmacology societies and industry are joining forces to create appropriately trained in vivo pharmacologists. One of the biggest initiatives has been launched in the United Kingdom; the British Pharmacological Society (Box 1) has set up funding with all the major UK pharmaceutical companies for around ten universities to run in vivo pharmacology modules. Students take time out (usually in their third year) and are given experience in the skills required for in vivo work. In addition, UK pharmaceutical companies also fund students to go on 'sandwich' courses. In the United States, Merck are collaborating with the American Society for Pharmacology and Experimental Therapeutics (ASPET; see Box 1) to award postdoctoral fellowships in integrative pharmacology (the guidelines of which will be posted on ASPET's website soon).

Sir John Gaddum wrote1 almost 50 years ago (Gaddum, J. H.: The science of pharmacology. Nature 173, 14–15, 1954) that a pharmacologist can be described as a "jack of all trades", borrowing and building from all disciplines. His message is as relevant today as it was then — the type of skills that industry is looking for are a thorough grounding in physiology, physical chemistry, biology (including molecular biology) and therapeutics followed by high-level training/understanding of drug distribution and action. Developing skills and techniques in this field will be invaluable in helping companies to translate the glut of data spewing out from new technologies into new drugs.

IVP has a programme collaboration, DIM, with the graduate programmes:  Molecular Mechanisms of Disease (MoMeD) & Drug Research Academy (DRA).