25 Interviews for the FNP?s 25th Anniversary. The Foundation for Polish Science (FNP) celebrates its 25th anniversary this year. To mark the occasion, we have invited 25 beneficiaries of our programmes to tell us about how they ?practise? science. What fascinates them? What is so exciting, compelling and important in their particular field that they have decided to devote a major part of their lives to it? How does one achieve success?
The interviewees are researchers representing many very different fields, at different stages of their scientific careers, with diverse experience. But they have one thing in common: they practise science of the highest world standard, they have impressive achievements to their credit and different kinds of FNP support in their extensive CVs. We are launching the publication of our cycle; successive interviews will appear regularly on the FNP website.
Some People Enjoy Hard Tasks
Bernadeta Szewczyk, PhD, a neurobiologist, talks to Anna Mateja.
ANNA MATEJA: Depression is a disorder of modern-day people living in a world of accumulating and therefore mentally overwhelming information and impressions. Your research leaves the macro scale, namely the social environment, in order to focus on another aspect of this disorder: what happens at the molecular level that causes people to lose their joie de vivre.
BERNADETA SZEWCZYK: The question of the mechanisms of depression, i.e. what goes on in the brain of someone suffering from depression, is the foundation of our research. According to one hypothesis, the synthesis of neurotransmitters in the brain, mainly serotonin, dopamine and noradrenalin, is reduced. Another, slightly later hypothesis suggests that symptoms of depression are the effect of a disturbed balance between glutamic acid (an excitatory neurotransmitter) and gamma-aminobutyric acid (an inhibitory neurotransmitter). Research is also being conducted on the role of inflammation and immune system disorders in the development of depression.
That is not all; learning about the mechanisms determining the development of depression is still one of the more relevant scientific problems. The team on which I work, for example, is studying the role of zinc deficiency in the occurrence of depression and the role of zinc supplementation in treating this disorder. All this work has one purpose: the knowledge gained about the disorder could enable us to develop more effective, safer and faster-acting medicines.
Contrary to psychiatrists, you do not work with patients.
That’s true, but thanks to collaboration with clinicians, in our research we can use blood serum from patients with diagnosed depression and from healthy people. The goal of our investigations is to identify markers of depression that would help diagnose the disorder, settle on a therapy and control the effectiveness of the treatment. Other valuable material for research includes post mortem brain tissue harvested from deceased patients who suffered from depression (there are a few banks of such tissue in the world today). Together with material for research we receive a “case history” with the most important information about the duration of the disorder or the medication that the patient took. Thanks to this we can correlate the changes occurring at the molecular level with the patient’s condition at the time the tissue was harvested. This enables us to draw conclusions on the pathophysiology of depression or the mechanisms of action of antidepressants.
The need to find markers, modelled after those found in cancer diagnostics, would suggest that depression as a disorder eludes both doctors and researchers.
The disorder is diagnosed on the basis of a patient interview (the questionnaires are very detailed and enable the patient’s condition to be assessed already during the first visit), and specific clinical scales are used to evaluate the patient’s condition. Markers could confirm such a diagnosis or help select an effective therapy. As shown by research, including that of our team and the clinicians working with us, one potential marker of depression could be the concentration of zinc in blood serum. It has been shown that it is much lower in depressed patients compared to the level of this element in the blood serum of healthy people. Furthermore, it was found that the concentration of zinc in drug-resistant patients is lower than in patients responding well to treatment. Scientists are also investigating the potential correlation between zinc concentration and how advanced the disorder is.
Zinc is not random here. I’d like to remind whoever left school a long time ago that zinc is responsible, among other things, for the proper functioning of the immune and nervous systems, for the body’s growth and development. Why was this element selected as an aid in fighting depression?
The idea to investigate zinc and determine its role in depression emerged thanks to research from the 1990s showing the antidepressant properties of compounds that inhibit the NMDA receptor (a glutamate receptor). Zinc can have an inhibitory effect on this receptor. To clarify, allow me to explain that in this context receptors are specialized proteins through which neurotransmitters, e.g. glutamate, affect cell processes and consequently the body’s functions.
The initiator of this work was Prof. Gabriel Nowak, whose team I joined in 2000. The first studies enabled us to determine the antidepressant properties of zinc. Further research proved the efficacy of zinc supplementation in improving the effectiveness of classic antidepressants. Next, in collaboration with the Clinic of Psychiatry at the Jagiellonian University Medical College, we investigated zinc levels in the blood serum of a selected group of depressive patients. Our research as well as studies conducted at other centres, including epidemiological studies from recent years, showed that low zinc levels increased the likelihood of depression and hindered the body’s response to treatment.
The results I have described are the effect of research conducted for over 15 years. Knowledge on zinc itself and its role in the body has increased substantially during this time. Starting from the general knowledge that the efficient functioning of the human body depends on the appropriate amount of this trace element, information was gathered showing that zinc in the brain could play a significant role in signal transmission in cells. Proteins responsible for maintaining homeostasis, i.e. a stable level of zinc and its specific receptor, were discovered and described. However, new questions appeared: What role do these proteins play in depression? How does a brain functioning with a zinc deficiency change? How can the brain zinc level be reliably assessed? We also keep coming back to more fundamental issues: Why does zinc have an antidepressant effect while its deficiency causes the effects it does? Does it affect the level of the aforementioned neurotransmitters? This is all very interesting, because each question implies something new that will lead scientists onwards.
Onwards to more question, because it is clear from what you are saying that any answers turn into more questions, but more precisely posed.
And to think that I got involved in this research by accident. I started working at the Institute of Pharmacology of the Polish Academy of Sciences ? at the Department of Neurobiology headed by Prof. Andrzej Pilc ? in 1997, a few weeks after graduating in biology from the Pedagogical University of Kraków. I wanted to be a teacher, but teaching practice at a school helped me realize that it wasn’t for me. I wrote my master’s thesis at a department that conducted laboratory tests. That’s where I changed my point of view: I wanted to work at a laboratory, not a school.
At the institute, I couldn’t choose the topics of my projects straight away. In fact, initially I performed technical engineering tasks, and did not become a research worker until a few years later. The team I joined studied the role of the glutamatergic system in depression.
I never abandoned my inquiries from that time, I only expanded them to include the role of zinc in depression, and I don’t regret it. Research on depression intrigues me just as strongly as it did almost 20 years ago when I first started working. But I don’t think I realized back then how much it was needed by society.
Almost 350 million people in the world suffer from depression (WHO data), in Poland it is 1.2 to 1.5 million.
It is one of the most frequent mental disorders. Its incidence ? also in increasingly younger people, which is worrying ? is on the rise. There are quite a number of antidepressants available, but pharmacotherapy doesn’t work as well as expected in all patients. The time of waiting for the effects is another problem. Positive effects are felt after two or three weeks of treatment, which means patients often discontinue it. That’s why research to develop more effective treatments is essential. Zinc supplementation, as research shows, could improve the efficacy of classical antidepressants. However, it’s too soon to say whether it will find application.
It’s a good thing that the attitude towards this disorder has changed over the past dozen or so years. Depression is not laziness or a passing melancholy, when it’s enough to “pull yourself together”. These are serious symptoms ? depressed mood, lower energy levels and fatigue, loss of interest and the ability to feel pleasure ? which only a doctor can deal with. Seeing a psychiatrist is no longer cause for shame. Equally important, especially when a patient doesn?t feel the benefits of treatment yet, is support from family and friends.
In 2005 you went away for a two-year postdoctoral fellowship at the Department of Psychiatry of the university in Jackson, Mississippi. There, you also worked on depressive disorders, your career progressed?
Not quite. After defending my doctoral dissertation I gave birth to a daughter and quite soon had to ask myself the question: science or family? Since my husband worked as a teacher at the technical college of forestry in Lesko, I decided to give up science and look for a job as a teacher. Things turned out differently. Prof. Nowak suggested that I work 3-4 days a week at the Institute of Pharmacology, carrying out the rest of my duties, such as analysing results and writing papers, at my home in the Bieszczady Mountains. I took the risk. My daughter was six months old when I went back to work.
I can only admire you.
It wasn’t a simple solution, but it worked because I had strong motivation and my husband’s support. The START stipend for young researchers, which I received from the Foundation for Polish Science in 2003, helped financially. Then came the proposal of a postdoctoral fellowship in the United States. We went there together. I ended up on a wonderful team of people thanks to whom I learned a great deal. Among other things, I took part in research involving post mortem brain tissue for the first time. For me, it was innovative then, but over there it had been used on a large scale thanks to “brain banks” of brains harvested from people who had decided to donate their organs to science after death. The research I conducted there focused on the role of the serotoninergic system in depression. Thanks to the fellowship I expanded my research interests: today my research field is the role of the glutamatergic and serotoninergic system in the antidepressant effect of zinc, and collaboration with the centre in Jackson continues.
Back in Poland, I returned to the Institute of Pharmacology, my family settled back in Lesko. Then our son was born.
And you asked your husband if he wouldn’t agree to stay home with two children?
Yes, I asked and he agreed, but it would have been much harder with two children. My husband, though he loved his job in the Bieszczady Mountains, decided that since I had achieved so much, we should organize our life around my job and not his, and that we would move to Kraków. We changed almost everything in our life, uncertain if it would be worth it but knowing there was no way out, because we had to choose. But as seldom happens, the reward for our efforts was not long in coming.
In 2013 I received support from the FNP under the PARENT-BRIDGE programme which helps parents with young children return to research. The project enabled me to become scientifically independent and launch research that had attracted my interest: on the role of proteins responsible for brain zinc homeostasis in the pathophysiology of depression. I received a grant from the National Science Centre in the same year, for research on the role of the serotoninergic system in the antidepressant effect of zinc, which in turn allowed me to continue my research begun during the postdoctoral fellowship. I ran both projects simultaneously for two years, additionally taking part in projects of the Department of Neurobiology. In terms of the time involved, it was very tough. I couldn’t work at the institute from six in the morning till late at night, as sometimes happened when my family was living in Lesko. This time, they were waiting for me.
What does science mean to you?
I’ll reply using an example: it’s afternoon, the institute’s labs and corridors are emptying because people are finishing work, and a colleague calls before leaving to ask “How are those tests of ours going?”. That’s science. You don’t get off work after eight hours, because you almost constantly return to it in your thoughts. Not because you have to; because you want to. The questions we’re concerned with are too interesting and the investigations so unpredictable that it’s hard to tear yourself away.
Scientists make a living by seeking answers to intriguing questions, but this requires many sacrifices and excellent organization as well as support ? to mention the kind of support provided by the PARENT-BRIDGE programme. I carried out the project for which I received support in collaboration with the Department of Psychiatry of the university in Jackson (it was thanks to them that I had post mortem tissue to study) and the Cytobiology Department of the Faculty of Pharmacy at the Jagiellonian University Medical College. The research involved students, who received stipends envisaged in the programme. For them it was an opportunity to see what scientific research was about. A few master’s theses were written during the project, some of the results were included in a doctoral dissertation, another one is in progress. The programme that was meant to be a bridge for me also became one for the young people I brought in to work on my research topic.
What sacrifices does science require?
Chinese researcher Prof. Hualan Chen, whose research on lethal flu viruses brought her one of the main prizes in the worldwide L?Oréal?UNESCO for Women in Science competition in 2016…
In that competition, you received a distinction in the International Rising Talents category for your research on depression.
That’s true, but returning to Prof. Chen, she admitted that she had no other hobby besides science. She devotes herself completely to her work, her family accepts it. I understand her.
Would you be able to do that? Or want to?
No; another prize-winner admitted that she didn’t have a family so she had results and could laugh. Why? Because she had no qualms of conscience about working at anyone’s expense. But for me my family is a form of escape.
One that enables you to laugh?
Exactly, because they tear me away from thinking about work. They introduce a balance in my life, even when there are reproaches: “Mummy, why do you get back so late?”? But I have someone with whom to share my worries and my joy at new achievements.
BERNADETA SZEWCZYK, PhD (born 1973 in Rabka-Zdrój) works at the Institute of Pharmacology of the Polish Academy of Sciences. A beneficiary of FNP programmes: START (2003/2004), PARENT-BRIDGE (2013).