Switzerland’s Quest for Alternatives to Animal Testing of Pharmaceuticals

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Animal testing for medicinal purposes is back under the spotlight in Switzerland after a petition against the practice filed in Bern managed to generate tens of thousands of signatures. Even more ominously, a popular initiative emanating from the Canton of St Gallen is still pending that proposes an outright ban on all such experiments and has already garnered the backing of more than 80 organizations.

 

Increasing Unease

The country has long been considered fertile ground for animal welfare activists given its penchant for direct democracy and the relative ease with which pressure groups of all stripes and colours can propose legislation and have it put forward to a public vote. Indeed, similar popular initiatives to curtail animal testing have already been held (and resoundingly rejected) in 1985, 1992 and 1993 respectively. What is perhaps different this time around is the intensity of feelings on both sides of the debate, as well as the potential implications for Swiss innovation in the pre-clinical testing arena.

Proponents of a ban, either phased or outright, highlight not only the suffering that animals are subjected to during the testing of new medications, but also the inefficiency of the process as witnessed by the high attrition rates during subsequent clinical trials where a large majority of drug candidates fail to make the grade. Their members, which include some representatives from the Social Democratic Party (SP) and the Greens, would like to see their country turn its back on animal trials and instead become a champion of alternative drug testing mechanisms.

 

Too Much at Stake

Naturally, the proposal stands little chance of ever making it into law with most stakeholders attuned to the damaging consequences that a ban would have for public health and the economy, not to mention Switzerland’s globally renowned biomedical research reputation. Scientists, clinicians and the academic community, for instance, argue that, under such constraints, the country would lose research expertise, become unable to contribute to the development of new and innovative drugs and risk an exodus of highly qualified researchers.

While we, of course, appreciate that these proposals are motivated by the understandable intention to improve animal welfare, they would make it virtually impossible to continue developing medicines to treat diseases and thus cause unsurmountable problems for society just at the juncture where it faces enormous healthcare challenges

Matthias Egger,  National Research Council.

“While we, of course, appreciate that these proposals are motivated by the understandable intention to improve animal welfare, they would make it virtually impossible to continue developing medicines to treat diseases and thus cause unsurmountable problems for society just at the juncture where it faces enormous healthcare challenges,” affirms Matthias Egger, President of the National Research Council. “Our nation’s supply of Covid-19 vaccines would be jeopardized, as would the supply of any of the existing medication against Covid-19, all of which have been developed using animal experiments,” he warns.

A blanket ban would also endanger a fundamental pillar of the national economy, forcing in-country pharmaceutical players to re-patriate large parts of their operations. Constituting over 47,000 jobs in 2020, the pharmaceutical industry is not only a major employer, but directly contributes a full 5.4 percent of GDP and accounts for 45 percent of exports making it an essential ingredient to the nation’s prosperity.

Even the oldest and best-known animal rights organization in the country, the Swiss Animal Protection (PSA), has spoken out against the controversial proposal. They consider animal testing to be a necessary sacrifice to protect health and the biosphere by ensuring that dangerous substances do not make it onto the market and into the environment. Other animal rights activists have also questioned the wisdom of forcing animal testing abroad and away from proper oversight, control and scrutiny. Many recall an unfortunate episode in 2019 when Zurich-based Inthera Bioscience made headlines for outsourcing animal testing of their products to Germany for what resulted in highly stressful experiments with catastrophic consequences.

 

An Ethical Benchmark

Interestingly, Switzerland already possesses some of the most stringent animal welfare legislation on the planet. For many, the country is regarded as a gold standard in how to conduct research ethically. The current legal framework stipulates that each and every animal experiment must be authorised by dedicated cantonal animal experimentation commissions, and that a weighing of interests be carried out on a case-by-case basis. A robust supervisory regime is also enshrined in law with view towards keeping the number of animals experimented upon as low as possible and experiments free from excessive stress. Accordingly, labs conducting experiments are obliged to report the number of times they have used animals and have to submit the results of all completed experiments.

These regulations certainly appear to have had an impact in reigning in unnecessary animal experiments. Figures from the national office of statistics demonstrate that, while almost 2 million animals were used per year in experiments in Switzerland in the early 1980s, the number has declined to around 570,000 these days. There have been changes to the type of species used too with far fewer tests on monkeys. 80 percent of the animals now comprise mice and rats and are primarily deployed in basic and biomedical research with the aim of better understanding diseases. In 2019, primates accounted for a mere 0.05 percent of all species.

Perhaps the most eye-catching element of the Swiss Animal Protection Act is the principle of the 3Rs: Replacement, Reduction, Refinement. This is a concept that has been gaining credence around the world and mandates that researchers and drug investigators must replace animal experiments in scientific research with alternative experimental methods as far as possible; reduce the total volume of animal experiments and the number of animals per experiment wherever practical via results pooling; and refine their methodologies and trial design to minimise stress and strain.

It is in this area where the ongoing debates may have repercussions. In an effort to appease the animal rights lobby, Swiss parliamentarians recently voted for an additional CHF 12 million to upgrade their dedicated national 3R Competence Center, as well as for a new nationwide research program to promote 3Rs starting this year, for which some 20 million francs will be made available. Developments like this may well position Switzerland front and centre of international efforts to rethink and reconfigure the pre-clinical trials testing phase of drug development.

 

Bioprinting, Organisms-on-a-Chip & Organoids

Swiss companies are also increasingly active at the vanguard of efforts to trial alternative technologies that would potentially render animal testing obsolete. Certain companies have been experimenting with 3D printing techniques and the use of bio-inks to replicate the 3D structure of a human tissue. Ever since the EU banned animal testing in cosmetics research back in 2013, the French giant L’Oreal and US biotech Organovo have been striving to bioprint human skin for testing. Now companies such as Ticino-based start-up TissueLabs seem to have picked up the baton and are beginning to apply similar technologies to the drug development space.

Complex drug efficacy and safety tests that used to take months using conventional animal testing now can be carried out on our microfluidic device in merely a handful of days, at a fraction of their current cost and in a fully automated manner

Matteo Cornaglia, Nagi Bioscience

Meanwhile, another Swiss actor, Nagi Bioscience, a spin-off from the Ecole Polytechnique Fédérale de Lausanne (EPFL), has been pioneering the development of ‘organism-on-chip’ technology – an altogether different approach thar combines microscopic worms and microfluidics as a sustainable alternative to traditional animal-based biomedical testing. “Complex drug efficacy and safety tests that used to take months using conventional animal testing now can be carried out on our microfluidic device in merely a handful of days, at a fraction of their current cost and in a fully automated manner,” enthuses the company’s CEO and founder, Matteo Cornaglia.

The growing of cells and organoids – clusters of cells with a similar structure to internal organs – in the laboratory represents yet a third alternative approach. Lausanne-headquartered Sun Bioscience, for example, has been using organoids to model the intestine and study how it is affected by different substances.

Taken together, these diverse approaches are both emblematic of Switzerland’s enduring capacity for ground-breaking innovation and the seriousness with which the local pharma and scientific research communities are setting about trying to reimagine and improve upon one of the more notorious stages of the drug development cycle.

 

Here to Stay

That is not to suggest that in-country animal testing will be abandoned anytime soon, however. While early-stage technologies such as organoids and organisms-on-a-chip are undoubtably helping to make in-vitro research a better predictor of drug effects, they still only act as models for real biological processes.

“Testing drugs on laboratory-grown cells or tissue cultures remains a long way off. An organism must be examined in its entirety in order to find the desired and undesired effects before it can be released to the population. You simply can’t achieve that with individual cell clusters,” affirms Detlef Günther, Vice President for Research at ETH Zurich.

 

 

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Image: Paul Klee. Insula dulcamara (1938)
Source/Photographer: http://www.sai.msu.su/


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