We think of viruses as villains who can infect us and cause serious problems. However, not all viruses are the same. Yeast viruses are broadly found in nature, and they are studied at the VU Life Sciences Center (VU LSC) by biochemist Prof. Saulius Serva's team. "Yeast viruses are a different matter. [...] From an evolutionary point of view, such viruses should have disappeared long ago. [...] But if something exists in nature, it obviously deserves its very own place", says the professor about his main research interest.
It turns out that certain parts of viruses can also be used for extremely precise drug delivery, with fewer side effects, but a greater impact. "Many of the drugs we use are prescribed for a disease, but they don't target the diseased organ. This means that they are injected into the blood and circulate there. How long do they stay there, where do they go - somewhere purposefully, somewhere blindly. The side effects are significant and poorly managed", says the researcher.
With Prof. Saulius Serva, we talked about yeast viruses and the possibilities opening up by their research, falsehoods, and the Lithuanian scientific system.
Prof. Saulius Serva
Q: There are cases when world-famous and distinguished researchers spread lies or even conspiracy theories. For example, the Nobel Prize laureate John F. Clauser, who denies the scientific consensus that anthropogenic climate change is occurring, and who has nothing to do with climate science. However, he is often quoted in fake sources because he has great authority - after all, he is a Nobel Prize laureate. Why do you think this happens?
A: There is such a term as "Nobel disease". The term was coined a little earlier to describe another researcher. There is no shortage of colorful personalities in science: one researcher received the Nobel Prize for a really worthy invention, started giving public lectures, traveling around the world with presentations, etc. In his opinion, the cause of AIDS is not the human immunodeficiency virus, he denied climate change and was interested in esotericism. When you reach exceptional heights, many people want to hear you and talk to you, and it can be tempting to talk on topics that are not necessarily within the scope of your competencies.
It's in human blood, still not everyone has audiences the size as of Nobel Prize laureates. Scientists must disseminate either sound knowledge or knowledge in a broad sense. But they are human being too, and when are given the opportunity to speak to a large audience, there is a great temptation to pass off one's personal opinion as a reliable knowledge. Although these are two different things, it can be difficult to control them.
Q: While working with researchers, I also notice scientific modesty: when they do not speak on topics if the latter does not completely correspond with the ongoing research. However, scholars understand academic sources and can critically evaluate data and information, even if it is not 100% exactly their research area. In your opinion, how do these extremes arise, that is, those who speak without competence and those who do not speak at all or speak on very narrow topics?
A: I think that many things can be listed here. Maybe it's academic solidarity. Objectivity is extremely important in science, which is ensured by peer-reviewing approach. Thus, speaking out on issues that are not entirely in your field, you can cause significant damage to a colleague or his work, etc., not to mention the credibility of the expressed opinion. These can be quite subtle but significant matters.
It is also important to mention that science has been undergoing many transformations in recent years, as paradigms change. According to the current practice, scientific articles are evaluated according to how many colleagues in the world quote them. However, now there are various the so-called predatory publishers who have figured out how to commercialize the quotation system. That is, to use the quotation system to get money, but not to give the value that was previously directly related to the quotation as a merit. For example, if the aim is to make publications available to the public as soon as possible, the author has to pay extra - this was not the case before. Now authors pay because they are interested in publishing, publishers are interested in accepting manuscripts because they need as many articles as possible; after all, so they earn more. And the only tool that allows those publishers to publish many articles is the imitation of objective evaluation (the so-called peer-reviewing). When there is no objective evaluation, the numbers of worthless publications increase, and quality does not rise out of quantity. On the contrary, the quality steps down.
In addition, where science is very competitive, for example, where there are hundreds or even thousands of applicants for the position of a professor, and only one has to be chosen, there is a huge pressure to publish as much as possible. When there is pressure to get as much published as possible, predatory publishers are there to offer the service.
Thus, the scientific system is out-balanced, and the most "guilty" of this, in my opinion, is the monetization of public access that allows unlimited dissemination, bypassing the quality criterion. We need to change the system, and come up with something new. The whole system of dissemination of scientific results is on the verge of breaking, and it is not clear which way it will go.
Q: You touched upon one more topic that I wanted to discuss: how do you assess the internationality of Lithuanian science?
A: The internationality of Lithuanian science... is not a completely correct concept. There is no such thing as national science. Science is impossible without internationality.
Science is based on wide dissemination of knowledge, cooperation, and peer evaluation. At the country level, if that country is, for example, the United States, it is possible to ensure dissemination, cooperation, some selection, etc. And on the scale of Lithuania, unfortunately, not.
Here, the only way is to participate in international scientific activities. Science must be distinguished from the imitation of science. National imitation of science is possible indeed, it is real. But science is international in its nature and basic operating principles. Only in this way can we ensure that it will be of high quality.
Q: What about the pressure on researchers to publish their works in Lithuania, compared to the Western world?
A: It must be noted that the modern scientific research environment in Lithuania has been developing for just a several decades. And in the democratic Western world, science has developed over centuries; so practices, general culture and tradition have been formed for centuries and refined the mechanisms that ensure effective development. One of such mechanisms, although the most ruthless but the most effective, is competition. Competition works precisely through the number of publications, alongside other aspects.
In Lithuania, compared to the Western world, internal competition is small. In addition, new scientific centers are being created, where scientists from different institutions come together to create something in common. VU LSC, Centre for Innovative Medicine, and Nature Research Centre are good examples. Such centers attract talents to Lithuania. International funding opportunities are emerging to attract researchers, such as Marie Skłodowska-Curie Fellowship, and various local foundations are being created: such as MJJ or the Future Biomedicine Foundation, which finance research and help researchers to better establish themselves in Lithuania.
Attracting talent requires infrastructure and finance. In this sense, the Western world has fantastic and almost inexhaustible possibilities, which are used very effectively. We are still learning a lot of things, we are still adopting good practices, because such an environment simply did not exist before.
When the LSC was established and so many researchers found themselves in one place, we began to rise to a new qualitative level. Publications in the Nature, Cell, or Science journals are becoming commonplace. Until recently, there were almost no Lithuanian publications in such journals. The opportunity to cooperate, learn one or another method, learn the opinions of colleagues, etc. - it is something that was not very common in Lithuania before the creation of the LSC.
When it comes to financing, financial provision is extremely important. I will give an example: the "Human Genome Project" lasted for 13 years and was officially completed 20 years ago, although the final data of the complete human genome sequence were published only two years ago. The Americans estimated that the value of the project was approximately 3 billion dollars. Quite an insane number for a single scientific project, especially for the one that started back in the XX century. However, it was also calculated how much material benefit there was from that project. It turns out that $141 was earned from each dollar invested.
Now if you ask the members of the Seimas (Parliament of the Republic of Lithuania) whether they would invest 3 billion to a project that would one day earn much more. They would probably say they would invest. But if we asked if they would invest in a genome sequencing project... I think the answers would change. I believe that members of the Seimas who are doctors of science or interested in science would probably answer positively, but the final number of those who voted "for" would be regrettably small. Those nations that are able to look ahead, which think not only tactically, but also strategically, always win in history. And in our political field, it is difficult to see strategic thinking on science. I think it would be useful for politicians to have more understanding of how science works, how it is organized, how it is developed.
Q: It is said that political will comes from society, therefore it is necessary to explain to it how much, where, and why state money is invested. What place do you think education and science communication play in helping the public to understand how the scientific process works?
A: I believe that eventually a positive result will be obtained through education.
The coronavirus pandemic and quarantine have highlighted the part of society that rejects modern science. However, the vast majority still found out and maybe even learned something new.
Communication was key in the management of the pandemic, as it is in the context of any other such major shock event. Communication must be professional, but at the same time understandable to the public, and information accessible. Probably, it is precisely the availability of information that we lacked, especially the deficit of wide and reliable information dissemination channels.
It is necessary to present researchers to the public, what problems they solve, to ensure a constant flow of knowledge and the reliability of that knowledge in order to leave no room for speculation, fantasy, political or personal interests. People can be manipulated quite easily with modern means of communication.
For example, I attended a conference in Spain, and in the hotel, I turned on the Russian propaganda channel RT out of curiosity. I listened to it just a couple of times and started thinking whether I’m getting out of my head. If you spend enough money and do it professionally, people's opinions can be swayed either way.
Q: Now I would like to talk about your research with yeast viruses. Why did this topic interest you and why is it important for us to expand fundamental knowledge about such viruses?
A: Researchers are often interested in either a specific research object or discover a problem they want to solve by asking certain questions. It happened to me that those two things somehow came together. We know viruses as destroying everything, annihilating everything... like some uncontrollably multiplying horde. Yeast viruses are a completely different creature. It is a component that does not kill the cell and does not leave it - it lives in it. Yeast viruses are therefore a very unusual entity. And I had and still have many unanswered questions that stimulate intellectual curiosity.
Viruses have been intensively studied since the end of the XIX century, beginning of the XX century, and it was their research that gave birth to modern molecular biology in the middle of the XX century. Virus research has magically linked the biological phenomena driven by viruses to their molecular, mechanistic cause.
As I’ve mentioned, yeast viruses do not kill host cells. They spread only when the cell divides, there are no other ways to transmit these viruses. From the evolutionary point of view, viruses that do not kill or leave the cell should have disappeared long ago. Therefore, the mere understanding, the mere fact of the existence of such viruses is interesting enough.
We still don't understand exactly how yeast viruses evolve. We have some data that they are very closely related to the protein synthesis of the cell, to ribosomes, and so on. Perhaps this is the mechanism that ensures the survival of these viruses.
Viruses as organisms are incredibly interesting. They are called non-cellular life forms, although that term is rather an oxymoron - we know that life is based on cells, and here is the universally accepted definition of non-cellular life form.
Q: Are viruses still considered a form of life?
A: Yes, it is a non-cellular form of life. But certainly no less interesting than cellular life.
Why a life form and not some kind of appendage? The world of viruses is diverse, we know some that are even simpler, just molecules, but they are able to reproduce, cause diseases, etc. And they consist of one single molecule of genetic material. But if something exists in nature, it obviously deserves its place.
While studying yeast viruses, we noticed that they are very simple in structure. Their shell - the capsid - is made of single type of protein and forms a perfect sphere of 120 protein molecules. These are particles with a size of 30–40 nm, which according to their size fall under the standard definition of nanoparticles. Nanoparticles are used in a variety of ways: for example, they are being used for targeted drug delivery. We conduct such research.
Q: What kind of drug transfer are we talking about?
A: For example, cisplatin and similar compounds are used in chemotherapy: they are injected into the bloodstream and work at the level of the whole body. Work has been published that describes the possibility of packaging active substances into nanoparticles that will ensure targeted delivery exactly where they are needed.
Many of the drugs we use are prescribed for a disease, but do not target the diseased organ. This means that they are injected into the blood and circulate there. How long they stay there, where they go - somewhere purposefully, somewhere blindly. The side effects are significant and poorly managed. Therefore, an important goal is to achieve as few side effects as possible, but as much effect as possible.
This can be achieved by targeting drugs to a specific organ. Protein structures, nanostructures, can be genetically modified by attaching anchors that direct drugs to the required organs, cells, or even a specific cell location. We already have preliminary data showing that nanoparticles can do this. Not all, of course. Therefore, we're trying to understand which parts of the mammalian cell the nanoparticles we're designing go to, and how to control that targeting. We are studying both the fundamental part of the processes and looking for specific application possibilities.
Q: And how wide is the field of application of these nanoparticles?
A: For now, we are evaluating the possibilities and testing various combinations of particles and active compounds. If we see that it can work, the horizons will be very wide, but it is still too early to predict which direction we will go. Only imagination and technical possibilities set up limits, but the field of applications is very wide. Now that we have seen that nanoparticles do enter mammalian cells, the next step is animal studies.
What we have already tested is antibacterial peptides that act on gram-positive bacteria, which are the source of food contamination. We can package an antimicrobial peptide called nisin and transfer it to a culture of bacteria, which we destroy. This is how we demonstrated that we can package a biologically active material and transport it to where we need it. Now we are going further and expanding the research field.
Q: Regarding the future, what question would you most like to find an answer to?
A: The one I don't know yet (laughs). Science is constantly renewing itself, and questions arise from what we already know. So I still don't really know the question that I would like to answer the most. On the other hand, if I have already answered that question… then what’s next? All done then, right? For me, it is a continuous process, successful experiments give birth to new questions and new challenges.
Q: Thank you for the conversation.
A: Thank you.
Interviewed by Goda Raibytė-Aleksa
Photo credits: VU LSC archive