Acta Scientific Pharmaceutical Sciences (ISSN: 2581-5423) Volume 4 Issue 1 January 2020 Short Communication Swedish Model of Developing Innovative Drugs: What Happened and Why? Jan Olof G Karlsson* Received: December 12, 2019 Division of Drug Research/Pharmacology, Linköping University, Linköping, Published: December 23, 2019 Sweden © All rights are reserved by Jan Olof G *Corresponding Author: Jan Olof G Karlsson, Division of Drug Research/ Karlsson. Pharmacology, Linköping University, Linköping, Sweden. DOI: 10.31080/ASPS.2020.04.0463 - cacious drugs. It has for example been an explosion in our un- American collaborator Sterling Winthrop wanted to add “physi- Still there are large medical needs that are not met with effi it came to the final formulation of Visipaque, Nycomed Imaging’s derstanding of cancer biology but our ability to translate these ological concentration of calcium ions” to it, apparently because it advances into therapies is poor [1]. To developing new drugs is, would sound god when promoting Visipaque. Almén together with a few other scientists realized that such a formulation would put theoretically as well as practically, integrity, creativity, engagement, patients, particularly during coronary angiography, in real danger however, far from an easy task. It demands scientific competence, responsibility and, not at least, critical thinking. - because of increased risk of ventricular fibrillation. The Manage - arguments but not Almén! Later on competitors argue but without cover and develop new drugs that met large medical needs, e.g., ment of Nycomed Imaging was ambivalent for Sterling Winthrop’s Before 1990, the Swedish pharma industry was efficient to dis any proof that Visipaque was more nephrotoxic than its forerun- terbutaline (Bricanyl), felodipin (Plendil), metoprolol (Seloken) ners. Knut Joakim Berg on the other hand was convinced from his and omeprazol (Losec), together with several others. The research clinical experience with Visipaque that it was less nephrotoxic. This organizations at Draco and Hässle, who developed these best-sell- was a critical issue for Visipaque and Nycomed Imaging once again was ambivalent but Berg managed to convince them to conduct a innovative capability. Terbutaline was actually discovered before ers, were small but with great scientific competence, creativity and study. This study published in New England Journal of Medicine [3] showed exactly what Berg had predicted, i.e., Visipaque was less communication from my opponent professor Torsten Olsson at my β-adrenoceptors were divided into β1- and β2-receptors, personal nephrotoxic than its forerunners. As a result the sale of Visipaque public defense of the PhD thesis. Olsson was central in the terbu- increased tremendously. taline project. In 1967 Lands reported that there were two types [2]. However, very soon after the launch of Visipaque the President agonist. At that time the same person often followed the drug all of Hafslund Nycomed (the mother company of Nycomed Imaging) of β-adrenoceptors, β1 and β2 Terbutaline is a selective β2 the way from discovery to marketing. As preclinical member of the Svein Aaser announced in an extra issue of the internal journal of iodixanol (Visipaque) team I experienced the same culture in Nor- Hafslund and Nycomed, AGENDA, that Nycomed Imaging was go- way. I started working for Nycomed Imaging in Oslo 1992 and Visi- ing to merge with the American IVAX Coperation (see front page of paque was launched 1995. It was really exciting to be a member of Agenda). This was apparently a company nobody had heart about the project group during the early marketing period, which among and a majority of owners stopped the merger. However, two years other things included teaching the sales organization of Nycomed later Nycomed Imaging merged with Amersham, at a 55%/45% Imaging why Visipaque was a better x-ray contrast medium than bases. At that time Nycomed Imaging had at least three big products its forerunners. This was far from an easy task taking in consid- (Omnipaque, Omniscan and Visipaque), whereas Amersham only eration the success with its forerunner iohexol (Omnipaque). In- had one (Myoview). Nevertheless, this started an era of molecular terestingly, Nycomed Imaging still in 1995 worked in accordance imaging with a strategy of putting radioactive technetium on recep- to the “Swedish model” (see below), whereas Swedish companies tor selective antagonists in order of image pathological upregula- long before had left it and gone into the mega-merger era charac- tion of, e.g., membrane angiotensin II receptors of the heart. Every terized by a never-ending reorganizations of R&D. In addition the receptor pharmacologist should realize that this is a mission im- small Swedish companies, and also the Norvegian companies, had possible, due to a very low concentration of membrane receptors. a close collaboration with outstanding Swedish and Norwegain On the other hand membrane receptors are ideal target for therapy, researchers, such as the professor of pharmacology Arvid Carls- son (1923-2018; Nobel laureate in physiology or medicine 2000), cardiovascular diseases. The company was then bought up by GE e.g., subtypes of β-adrenoceptors and angiotensin II-receptors in professor of radiology Torsten Almén (1931 – 2016) (see photo) 2004 and became GE Healthcare. In the coming years, more or less and professor of nephrology Knut Joakim Berg (1930-2017). When all research activities moved away from Norway. Citation: Jan Olof G Karlsson. “Swedish Model of Developing Innovative Drugs: What Happened and Why?". Acta Scientific Pharmaceutical Sciences 4.1 (2020): 55-58. Swedish Model of Developing Innovative Drugs: What Happened and Why? 56 cations, have been increasingly important [6]. Few of them in the - B&D-driven pharma are able to write scientific articles, and hence few are able to read scientific articles and draw appropriate conclu - sions in the company’s field of interest. Every complicated matter lieve they understand the problem. Consequently, the inverse rela- is simplified in a way that makes the Board and Management to be tionship between invested money and productivity in the pharma- ceutical industry has for many years been a reoccurring theme. For - ingly challenging and expensive, and consequently extremely more Big Pharma, finding new blockbuster drugs is becoming increas expensive for the society. Interestingly, since 2013, smaller enter- prises have increased innovation and delivery, bringing a dispro- portionate amount of new products to the market (https://www. pharmalive.com/annual-report-2019-top-10-pipelines-to-watch/) and bringing new hope for the future. However, of all thousands of Bio/Medtech companies founded, the great-great majority has generating the necessary revenues to survive. This, however, has failed in terms of finding viable clinical drug candidates and/or in not prevented investors, founders, and company employees from science [6] becoming wealthy, regardless of the companies’ fates and/or their An absolute, or as prerequisite Mark Knopfler for an express R&D organization it, “money for to develop nothing”. new Front page of the internal journal of Hafslund Nycomed, drugs is a high degree of creative/innovative capacity. Conformity AGENDA, where President Stein Aaser announces the merger is probably the most dangerous enemy to innovation and creativ- (fusjon in Norvegian) with IVAX Corperation. ity. Creativity is something that evolves spontaneously and there is no manual on how to build a creative organization. B&D-driven guys seem to believe they can create creativity and innovation by - holding training courses on the subject, where they appoint ”cham- zations have gradually been replaced with business and develop- During the last 30 years, or so, scientifically driven R&D organi pions” to inspire others in the organization to be more creative and ment (B&D)-driven organizations in the pharma industry, where innovative. My own experience is that this particular approach has the opposite effects, i.e., it destroys creative and innovative capacity throughout the whole chain of drug development [5,6]. However, the question about profit has become increasingly important - industry view in the mid-20th century, when George W Merck, the among scientists that still have it. To increase scientific competence the profit as the B&D-define it is rather different from the pharma pointed. These Boards typically consist of payed external experts. president of Merck and Co., noted that “We try never to forget that in the B&D-driven organization, scientific advisory boards, are ap However, in opposite to Arvid Carlsson and Torsten Almen, and - Knut Joakim Berg, these external experts rather typically consist low, and if we have remembered that, they have never failed to ap- medicine is for the people. It is not for the profits. The profits fol of yes-men. The aim here seems explicitly to legitimize the ideas pear. The better we have remembered it, the larger they have been” of the B&D-driven guys, particularly when it comes to interactions (Merck, 1950) [6]. with responsible authorities. This has resulted in a situation where Critical scientists in B&D-driven organizations have either to the pharma industry has lost most of its pharmacological/physi- ological competence that is needed to succeed in developing new drugs in the real world. leave the company or fully adapt to the B&D’s way of “developing” of working is typically seen upon as disloyalty from the Manage- innovative drugs. Criticism from scientists against the B&D’s way Market analyzes of how much a fancy drug is going to sell for are ment. This is of course strange in an activity that describes itself - as a knowledge-based one. A situation probably best explained by inherent conformity, as described by the Asch paradigm [7]. The afflicted with great uncertainty. This and ongoing blockbuster hys productivity of innovative drugs in Big Pharma [5,6]. main body of knowledge in creative/innovative-based industry is teria are most probably involved in today’s disproportionate low expected to be found among its scientists and not in the Manage- Another apparent cause to low productivity is the B&D-driven ment.