Researchers Were Able to Come Together
The BIOCEV, Biotechnology and Biomedicine Centre, started helping to test samples at the beginning of the pandemic. “It was an example of great solidarity and social cohesion,” says Pavel Martásek, Director of the Centre. According to him, the pandemic showed that it is science that gives answers, not politics.
How was Czech scientific research before the pandemic?
Thanks to national and European investments in large research centres, such as BIOCEV and others, the level of Czech science has been significantly increasing over the past decade. This is especially due to top equipment and instruments whose quality exceeds other similar organizational units around the world. Another milestone was the involvement of laboratories in international research consortia, which increases the level of their expertise and efficiency, and strengthens their importance within the international research environment. I am also pleased that we have managed to attract many scientific experts from abroad. This includes Czechs who left their home, so to speak, to acquire experience in another country.
And what changed during the pandemic in research, and did that time bring any positive impulses?
The covid pandemic has shown us that answers and solutions lie not in politics, but in science. In a very short time, scientific teams were mobilized to discover a huge amount of information about the new type of coronavirus. This helped us a lot both in our defence against the virus and in finding a way to attack it too. For example, intensive testing and sequencing as well as the rapid development and validation of new vaccines and drugs against covid-19 have been instrumental. During the pandemic, we witnessed an unprecedented situation and amazing international cooperation, with states investing heavily, with only one goal. As the saying goes – every cloud has a silver lining.
Will these positive changes persist even in times of peace, i.e. after the pandemic?
I firmly believe so. In connection with preparing for other possible pandemics, but also the development of more effective substances and vaccines, new investments can be expected in research in natural sciences such as biotechnology and biomedicine, especially virology, genetics, molecular biology, and the like. The current debate on the establishment of a national virology centre is proof of this, too.
The pandemic will end one day, but cancer, cardiovascular disease, diabetes, infectious diseases, a huge group of congenital genetic diseases and reproductive disorders will still remain. Anyway, I remain optimistic in this area of research as well. In the past, we were only able to describe these problems without being able to find their causes. Today, we can understand the cause of a disease, right down to the molecular level. Thanks to that, we are able to design a solution which, in the final phase, may lead to the development of effective medications or the discovery of a new therapeutical method, thereby saving many lives.
Has the private sector learnt to work with research? Have the researchers learnt to commercialize their results?
Although there are a number of legislative and administrative barriers in our country, the situation with commercialization and also collaboration with the private sector is improving. For instance, the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences systematically commercializes and converts the results of its basic research into practice. This includes, for example, Professor Holý's patents for antivirals. After research and education, the transfer of knowledge and technology is the third pillar at BIOCEV. Sooner or later, basic research leads to applied, practically usable outputs. This is clearly happening. One example is the development of a promising substance that directly targets cancer cell mitochondria and which has successfully passed phase I of clinical trials. Another is the definition of a new cancer medication category known as migrastatics that target metastasizing tumour cells.
What else would help to better link research and practice?
On the part of Charles University and the Academy of Sciences, the establishment of the Centre for Knowledge and Technology Transfer, or the Technology Transfer Centre of the AS CR, has certainly helped. Researchers do not have the opportunity to engage in consultations and enlist services in applying research results into practice. Both centres help scientific teams with specific cases of commercializing their results, analyse potential for practical application, provide intellectual property protection strategies and offer contractual cooperation with the application sector.
Anyway, increasing the level of awareness of the services and technologies offered to industry by Czech research centres would also contribute to greater interconnection. BIOCEV has already established a number of collaborations with the application sphere. These include, for instance, research into gene modifications, (pre)clinical trials of potential cancer drugs, the development of new vaccines, binding molecules, and many other projects.
To try to bring the pandemic under control, we need to know what mutations we are facing and how they are behaving. New mutations are revealed by sequencing samples. What hinders faster sequencing speeds and systematic sequencing?
No procedure to systematically collect samples from the population has yet been developed, sequencing is chaotic, and the results are not population-relevant. In this, we have to rely on healthcare facilities and the National Institute of Public Health (SZÚ), and it is difficult. The lack of metadata means we cannot enter the obtained data into databases, nor can we analyse them in depth from the epidemiological point of view. This problem has been around for quite some time.
BIOCEV runs sequencing but does not receive money from the government for it.
Yes, our colleagues from the Faculty of Science of Charles University in the BIOCEV centre have gradually been introducing sequencing and bioinformatics analysis protocols. So far, they are sequencing based on their own enthusiasm. Dozens of people have taken part in this work, and they have worked an estimated 350 hours voluntarily.
Only state-funded institutions will receive money for sequencing from the government. Private laboratories and universities will not. What are the effects of not sequencing more than we are now?
We will most likely miss an epidemiologically or clinically significant mutation of the virus, whether imported from abroad or "bred" here. Our sequencing clearly shows that the virus is changing. Almost every sample is unique, they differ in at least one letter. If a mutant starts to assert itself into the population, we need to find out as soon as possible so that we can intervene immediately, otherwise we may be surprised just like we were in January.
The need is to sequence five to ten percent of all positive samples. That is absolutely doable. We know that the capacities exist, and the cost is not high (approximately 2000 CZK per sample). It is essential to organize it well with the healthcare and private sectors and get paid for it.
In April, BIOCEV released information that you were ready for providing regular covid testing for companies, using PCR tests and saliva sampling. The price for companies was based on 400 CZK per sample. How did you manage to reduce the costs?
There are several factors. First and foremost, these savings are related to the self-sampling and sample registration performed by employees with the help of a reader and a code located on the bottom of each test tube. Researchers from the Institute of Biotechnology of the AS CR at the BIOCEV centre can also rely on the help of robotic systems, which eliminates demanding manual RNA isolation. With a volume of dozens of samples per week, the price for schools is 350 CZK, and for companies 400 CZK net of VAT per sample. Test results are available via a text message in just three to six hours. Another advantage is the certificate obtained for business trips abroad.
How many samples are you able to test via this method per month?
The current capacity of PCR testing at BIOCEV is 1,000 samples per day. Following the demand of companies and schools, we can increase this number to 2,000 samples per day.
The price for a PCR test at sampling centres is approximately 1 500 CZK, and it is assumed that these tests could be cheaper due to government restrictions. However, they could also become cheaper if they were used more, for testing company employees and children in schools, or if the government subsidized them. What is preventing PCR tests from being used more?
Now, it is mainly the cost, although the prices at BIOCEV are nearly comparable to antigen tests, and support by the government is still insufficient. In short – if you want to test, use antigen tests. If you want to detect those who are infected, use PCR tests. This is certainly a great lesson for revealing the waves yet to come, waves of any pandemics in their early stages.
At the end of March, together with the Biological Centre of the AS CR, you confirmed, based on a preclinical study in mice, that a new antibody developed by an international team of scientists from the Swiss Biomedical Research Institute is effective against the British, South African, and Brazilian mutations. The substance could work as a medication for those already infected, but also preventively as a vaccination. Can you tell us now, after the pre-clinical phase of the research, how significant a shift this is in combatting the pandemic?
It is really a very powerful tool that can block current mutations very effectively. However, the technology itself is important, because it allows us to adapt relatively quickly to other mutational variants of concern.
It is important that my colleagues from the Czech Centre for Phenogenomics at BIOCEV have developed a model for providing quick and cost-effective testing of not only antibodies, but also drugs and other therapeutic approaches against various SARS2 mutations. This is a unique contribution from our scientists, as they have provided the research community with a very powerful tool in the fight against the epidemic.
In the control group of mice treated with a monoclonal antibody, the virus mutated rapidly and became resistant within two days. The newly developed antibody is bispecific, meaning that it is a mixture of two natural antibodies. What makes it unique and what are its benefits?
The bispecific antibody is unique in that it combines two different antibodies into one molecule. This brings a number of indisputable advantages. First, this molecule targets two different points in the structure of the virus simultaneously, which prevents the virus from avoiding the antibody attack, and, at the same time, this prevents mutations, as it is very unlikely that the virus would mutate at these two points simultaneously. Second, this molecule replaces the need for an expensive mixture of natural antibodies at a fraction of the cost, making it the ideal candidate for treatment in poorer parts of the world.
Ordinary mice cannot catch the coronavirus. How did you make it work in them as well as in humans?
The researchers used another harmless virus that carried genetic information to make a specific human protein (Ace2), which SARS-CoV-2 recognizes as a gateway to human cells. Once the mice became infected with the virus, the cells in their lungs began to produce human protein, making themselves susceptible to infection.
When will the next phase of the research on this antibody, human clinical testing, begin?
At the moment, the Swiss team is already negotiating with a potential partner from the pharmaceutical industry. We hope that it will be possible to begin the human clinical study soon.
What has BIOCEV learnt from the pandemic? What have you learnt about yourselves and the world around you?
The pandemic has shown that we are able to respond quickly to global challenges. Together with other research institutes, we promptly participated in testing and significantly contributed to the management of the crisis situation. At that time, over one hundred volunteers from among BIOCEV’s employees signed up to help us. They helped both with infectious and non-infectious materials, isolation and RNA manipulation, the PCR method, administration, and logistics. A huge advantage was that they were already trained and had experience with the manual isolation of samples, detection, and operation of instruments.
It was a great example of immense solidarity and cohesion. BIOCEV was established to bring together teams of enthusiastic and well-trained scientists from six institutes of the Academy of Sciences and two faculties of Charles University, all working together under one roof. Due to the pandemic, mainly virology laboratories and research infrastructure of the Faculty of Science and First Faculty of Medicine at Charles University, and the Biotechnology Institute and the Institute of Molecular Genetics at the Academy of Sciences of the Czech Republic have worked together.
Source: Lidové noviny, June 5th, 2021, author: Markéta Rizikyová