1. Rapid test infrastructure and vaccine development
While the pandemic still seemed a long way off in Switzerland, researchers in Germany already developed the first test infrastructure for SARS-CoV-2 in January 2020. It took a few more weeks before the first wave of the virus swept across Europe. And in March, a market-ready test was already available from Roche. The test technology has since seen rapid improvements – testing for Covid-19 today is cheap, less invasive and also reliable. It took just one year before effective vaccines became available: the first effective vaccines were available at the end of 2020 and thus only twelve months after the pathogen was identified at the end of 2019. Usually, it takes between six and fifteen years from development through regulatory approval to market launch of a vaccine.
2. Reasons for the rapid progress
The rapid provision of test facilities and vaccines for SARS-CoV-2 can be attributed to three main factors. Firstly, the research community had already spent thirty years working on the mRNA technology that forms the methodological basis of various vaccines for the coronavirus; they were also able to fallback on other technical approaches and experiences. Secondly, there was a unique international collaboration between science, pharmaceutical companies and biotech start-ups. The various synergies that arose from this made rapid scientific advances possible. And thirdly, the regulatory authorities of various countries allowed a fast-track approval procedure. In addition to the key factors, basic research forms the cornerstone for all medical research. No medicines or therapies can be developed without exploratory university research which is conducted without any expectation of results and is also dependent on the use of animal experiments. A crucial element of medical research on substances is always the measurement of their safety and efficacy. Animal experiments are an indispensable method of testing these two factors – also in the case of vaccines and tests for SARS-CoV-2.
3. Research on mRNA goes back 30 years
Messenger RNA vaccines were discovered and developed over the last thirty years. Synthetically produced RNA is introduced to the cells of the body by inoculation. This RNA provides the cells with the blueprint for proteins which in turn trigger an immune response against the virus. RNA that enters a cell carrying information for producing proteins is called messenger RNA –hence the abbreviation mRNA. In the early 1990s, the Hungarian scientist Katalin Kariko carried out pioneering work on the development of therapeutic approaches using mRNA. Following a search for research funds that was initially fraught with problems, she succeeded in discovering a functioning immune response with the aid of synthetic mRNA together with research colleague Drew Weissman in the USA.
After her university career, Kariko continued the research at BioNTech. Her team was originally focused on vaccines against cancer, where mRNA specific for the occurrence of a cancer is produced for patients. But when the pandemic started, BioNTech and its partner Pfizer concentrated on the development of a vaccine against SARS-CoV-2. Instead of developing everything from scratch, BioNTech looked for the correct mRNA sequence for the production of a protein that triggers an immune reaction to the virus.
4. International collaboration
This rapid development of different vaccines is an extraordinary achievement that was made possible by an unparalleled international collaboration on all levels. Research-based companies had already gathered initial experience of dealing with coronaviruses with SARS-CoV-1 in the early 2000s – and MERS in 2012. As a consequence, the genetic code of the virus in the Covid-19 pandemic was deciphered early on. On the basis of the information available, various companies were able to begin work on the development of a vaccine. The collaboration between academic institutions and the pharmaceutical industry also served to accelerate vaccine development.
AstraZeneca, for example, developed a vector vaccine together with the University of Oxford. Successful cooperation between companies also had an impact: Pfizer developed an mRNA vaccine in collaboration with the German biotech company BioNTech. Johnson & Johnson developed a DNA vaccine using vectors in collaboration with its subsidiary company Janssen and its vaccines site in Bern. This vaccine, too, involves a new technology, which has already proved successful in vaccination against Ebola. With Lonza as a new production partner, Moderna was able to achieve a tenfold increase in the production capacity for its vaccines. As a result of this cooperation, Lonza in turn its expanding its facilities in Visp (VS).
5. Openness and flexibility of authorities
Aside from various forms of cooperation, accelerated and simplified procedures in the clinical phase also helped to speed up the review processes for the efficacy and safety of vaccines. Thanks to their openness to fast-track procedures, the authorities helped to ensure that the first vaccines were approved in record time. Despite the great urgency, safety (and efficacy) had and still have utmost priority. But producers were able to have various development processes running in parallel. This way, for example, different clinical trial phases could be combined. Pharmaceutical companies also recruited trial subjects simultaneously for different clinical trial phases. If one avenue of research proved unsuccessful, costly later clinical trial phases would have been redundant. The sharing of information between regulatory authorities was also stepped up and the approval process of Swissmedic was accelerated. Normally, the results of clinical phases I–III are collected and reviewed as part of the approval procedure. For an approval of vaccines against the coronavirus, however, individual studies were submitted to Swissmedic and reviewed in a rolling process. This delays in the process were avoided without any shortcuts when it came to safety.
The 30 years of experience in working with mRNA technology, the unparalleled international collaboration between the scientific community, pharmaceutical companies and biotech start-ups as well as the acceleration of regulatory procedures by the various authorities enabled vaccines to be developed in record time. But the pandemic has also shown us that, without the responsible use of animals, this would not have been possible.
6. Basic research is the cornerstone of all medical research
The production of vaccines in such a short space of time requires in-depth prior knowledge of countless molecules, substances and compounds. This is where basic research comes in. Basic research is not aimed at the development of a marketable product and remains open as to the results. Researchers are not looking for a specific property, but are interested in any effects. The substances studied provide the cornerstone for medical research. Of the countless substances that emerge from basic research, few make it to preclinical studies and clinical trials. Research on vaccines against SARS-CoV-2 thus began a long time before the virus was first reported. In the search for the right substance to combat the coronavirus, research teams fell back on substances investigated in the course of basic research. Every vaccine is based on tests with thousands of substances of which barely a few dozen were considered for the shortlist. This process is all part of preclinical testing.
7. Preclinical testing of safety and efficacy
There are primarily two criteria for exclusion that researchers apply to reduce the number of substances: efficacy and safety. Measuring these is a complex matter: the methodology ranges from computer simulations through testing with bacteria, cell and tissue cultures to tests in isolated organs. When all other avenues for testing have been exhausted, animal experiments are used. Every study involving animals must be approved by the cantonal veterinary authorities, who refer to the recommendations of the independent cantonal committees for animal experiments before deciding whether to grant approval, often with conditions, or not. For the protection of patients against serious side effects, animal experiments are required by law, before any clinical trials can be conducted. These regulatory animal experiments allow researchers to establish whether a substance is toxic and how long and how potent its effect is. A toxic substance can trigger diseases or cause genetic damage. From an ethical standpoint, therefore, a risk of this kind is unacceptable in the treatment of humans. The efficacy of vaccines is measured on the basis of the antibodies produced. Since current technology is not able to simulate an immune response in vitro – i.e. in a test tube – researchers must still resort to animal experiments for this, as animal experiments allow interactions of a substance to be studied in live organisms.
8. For medical progress
Without preclinical testing in animals, research into new medicinal substances would thus be unethical towards the human subjects in the subsequent clinical trial phases. The rejection of research using animals therefore prevents medical progress. However, researchers also have an ethical obligation with regard to the well-being of the animals. For this reason, pharmaceutical companies and scientific institutions in Switzerland follow the 3Rs strategy. In view of the incredible medical advances of the last few years, there can be no question of forgoing animal experiments: otherwise we would not have any vaccines now against the coronavirus nor effective therapies for cardiovascular disease, various forms of cancer and other serious diseases.