25 Interviews for the FNP?s 25th Anniversary: an interview with Dr Wojciech Fendler, medical doctor and researcher, by Anna Mateja

Dodano: :: Kategorie: 25 years Foundation for Polish Science
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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.

Pleasant reading!

A well-executed idea

An interview with  Wojciech Fendler, PhD,  medical doctor and researcher, by Anna Mateja

ANNA MATEJA: After medical school, why is it that instead of treating patients you decided to study microRNA?single-strand particles of ribonucleic acid that regulate the expression of genes?

WOJCIECH FENDLER: During my medical internship I became convinced that I am much better at analyzing data and conducting research projects than treating patients. During my studies I planned to become an anaesthesiologist. My first mentor, Prof. Andrzej Piotrowski, who now heads the Anaesthesiology and Intensive Care Clinic at the Children?s Memorial Health Institute  in Warsaw, showed me what an interesting but difficult challenge it is to work in an intensive-care ward for newborns. I treated seriously ill children, but I also participated in several interesting scientific projects. My internship finally made me aware that treating patients is not for me, because scientific questions interest me so strongly that I could not reconcile this with the pedantic checking (as that is how I like to work) of details in clinical practice. So of the three paths that open up for a graduate of medical studies?medical practice, research and teaching?I chose research and teaching.

Another important thing: when I received my degree in 2007, the funds that young researchers could apply for were already large enough that they did not need to starve. While it took me two unsuccessful attempts before I became a beneficiary of the START programme, which the Foundation for Polish Science targets to young people beginning their research careers, there were other projects supporting PhD students. Among other things, it became possible to hire young people under very good financial conditions in projects creating new research teams. This is how I became a member of the team of my second mentor, Prof. Wojciech Młynarski, head of the Paediatrics, Oncology, Haematology and Diabetes Clinic at the Medical University of Łódź, who took advantage of the Foundation?s TEAM programme. That time, which was a very good time to be a young scientist in terms of financial and scientific opportunities, urged me to focus on scientific work without worrying that I would have to earn extra money working shifts at the hospital.

What is so intriguing about microRNA?

Its role as a biomarker, a biological substance that enables diagnosis of the patent: to evaluate the presence and advancement of cancer. MicroRNA is a discovery of molecular medicine, which sees patients from the perspective of what is happening in their organism on the level of proteins, DNA and RNA. There are several thousand different kinds of microRNA (short, uncoded RNA) that are produced in cells and regulate how the proteins in the organism are created. MicroRNAs may be transported from cells to the bloodstream. We can detect several hundred microRNAs in the blood. From the amount of microRNA?or in scientific terms, increased or reduced expression?we assess if the patient is sick and the stage of the patient?s illness. MicroRNA acts like a messenger conveying information about the disease.

I first heard about its existence at a conference in Bologna, when I was working on diabetes and belonged to Prof. Młynarski?s team. At the conference I met scientists who presented microRNAs detectable in serum as a new class of markers in oncology. The topic was very fresh?not to say fashionable?and we managed to take it up quite quickly. We thought of using microRNA in identification of rare forms of diabetes. And because genetic diagnostics then were expensive, microRNA as biomarkers of these diseases could be a cheap and convenient tool. In December 2011 we filed the first grant application that would make the research possible.

You worked with monogenic diabetes, which occurs as a result of damage to a specific, identifiable gene. It affects about 5% of the 2 million diabetics in Poland.

After completion of the TEAM project focused on genetic epidemiology and identifying patients with typical monogenic diabetes, we shifted towards improving the screening process of selecting patients for genetic tests. Our goal was to identify these people by studying blood serum for the expression of specific microRNAs. In 2014, thanks to funding from FNP in the INTER programme, we expanded the validation group formed among patients in the UK. This means that apart from the group of Polish patients, to verify the results we conducted the same tests on a group of British patients. We also expanded the project by conducting additional research on the cell lines model. The research showed that the connection between the damaged gene disrupting the expression of microRNA at the cellular level and the changes visible in the serum is not an incidental association, but has the nature of a causal link. This is visible in the cells of the liver and kidneys.

The project also showed us clearly how dynamic the progress of molecular medicine is and how quickly the economic realities are changing. In the five years since beginning the work, the cost of studying the sequence of all genes coding proteins in the patient has dropped to a few thousand zloty. It is cheaper to conduct genetic tests on patients suspected of genetically based diabetes than to conduct a preliminary test based on serum biomarkers.

I find it hard to believe that this research could be regarded as wasted time.

Because it can?t. Biomarkers are helpful in any event?they allow for an initial screening of patients suspected of monogenic diabetes. Our research was the first of its type to be conducted anywhere in the world. And thanks to the systematically maintained register of monogenic diabetics, we now have the largest group of children in Europe diagnosed with this rare form of the disease. Because so far several hundred kinds of microRNA have been identified (it continues to be an interesting and intensively explored research topic), we are trying to use them in research projects?among other things in diagnosis of another rare disease, i.e. tuberous sclerosis, but also in a project that shows the changes occurring in microRNA during dialysis. And in other projects, where microRNAs are biomarkers showing the differentiation in types of brain tumours, or changes occurring under the influence of anti-cancer therapy. We also plan to work on lung cancers.

Your participation in these projects would not have been possible if you had not studied biostatistics. What good is it for a future doctor to have the ability to process large quantities of data?

I can explain this using the example of a single file sent from the Dana?Farber Cancer Institute at Harvard Medical School in Boston, which took me six months to process. It?s not huge. It contains data from 170 female patients who gave blood samples, sorted according to 220 variables. Somewhere in these columns was information how the microRNA profile of women with ovarian cancer looks. And I was able to capture it in this spreadsheet because I know which data provide information about the disease. Statistics are neglected in medical studies because after all it is the calling of a future doctor to diagnose illnesses and treat patients, and not to conduct difficult analysis of ?boring? data. But this example shows what is really going on in today?s world. It?s a handy tool that allows you to step back and think about all of the patients struggling with a certain illness and find the data that link them. Identifying these patterns leads us onward, to further research, and perhaps ultimately clinical applications.

Much more information is generated in medicine than we are capable of processing. Figuratively, there is probably a ?cure for cancer? lurking in these resources of data, but most of the data is not exploited and thus is useless. On the other hand, it costs the equivalent of some PLN 800,000 to create the file I am describing. It will cost just as much again to repeat these tests on another group of the same size.


Dr Wojciech Fendler by One HD

So we understand why analyzing data is not just a question of liking statistics.

But to assess it, it might be easier to create a group of molecular biologists and statisticians, furnished with grants, and a group of clinical patients of the right size, well described and skilfully treated. I received files of data from Boston or Warsaw concerning medical problems from neonatology or oncology to psychogeriatrics, which shows the scale of possibilities inherent in skilful analysis of data.

Since having my own Department?Biostatistics and Translational Medicine?I have been trying to mark out my own research fields. Topics that others are not exploring because they are too difficult or not interesting enough. One such area is developing a new diagnostic test exploiting knowledge of microRNA to assess whether a person given a high dose of radiation has a chance of surviving the radiation sickness. The degree of damage to bone marrow can only be assessed within a week after radiation treatment, which makes it hard to adjust the treatment to the patient?s condition. The research conducted in cooperation with team of Dr Dipanjan Chowdhury from the Dana?Farber Cancer Institute in Boston made it possible to develop a biomarker that assesses the extent of radiation within just a day of receiving the dose. With this information, for example on the scale of damage to bone marrow, a lifesaving transplant can be carried out sufficiently early. We published an article on this topic in Science Translational Medicine, a journal recognized in this field, which was featured on the cover of the issue.

Establishing cooperation with Dr Chowdhury was made possible by the MENTORING programme, launched by FNP with a view to young researchers working in Poland seeking to cooperate with scientists with major accomplishments in the given field. Because my biostatistics skills proved very useful to the researchers from Boston, over time I not only benefited from the help of my next mentor, Dr Chowdhury, but I also became a consultant to him.

What does it take to pursue successful science? Particularly when you have only the desire to learn, but are starting from scratch?

You can?t start from scratch on your own. First you have to find a mentor?someone who can assess the importance of the selected topic and the method of pursuing the goal. But first and foremost a mentor can say what not to do, knowing from experience that certain experiments don?t work and certain topics are only superficially intriguing. This is even more important because no one publishes negative results. So how is a novice supposed to learn that certain paths are foreclosed or unfeasible?

A mentor is the person you aspire to be?to know as much as the mentor and to be able to do what he or she can do. A model whose whole being testifies that the path you dream of can be pursued. But in your own way. The mentor teaches which direction to seek, but will not lead you there by the hand.

You mentioned three of your mentors. Can?t you have one mentor for your whole life?

No. If for no other reason, you can learn from your mentor only what the mentor is capable of, and you can?t duplicate someone else?s career. There?s no need to anyway, because there?s plenty of science to go around for everyone. Instead, while following your mentor, you need to look around you carefully, seeking new topics. The mentor understands that at some point the student will leave, even if that is hard to accept. But it is the natural order of things for a subordinate to evolve into a partner for debate and cooperation.

Apart from a mentor you also have to have funds for conducting research and to live on.

It seems to me that currently in Poland it is easiest to raise money for researchers under age 35, or those who have gained the position of a global leader in their field. It?s most difficult for people between 35 and 50 who are seeking funding from the same programmes as researchers over age 50, even though they find themselves in very different situations: these are scientists who are finishing their doctoral dissertations late, or have taken maternity leave, or are just before or after completion of their postdoctoral degree, or they are professors who have difficulty finding funding for their research. That?s how I see it as a reviewer of research projects seeking funding. From this perspective I have also observed for several years a gradual shifting of the centre of gravity in funding for science from experienced researchers to those making their debut. Consequently, young people are being saddled with managing projects, which means bureaucracy, which I think is inappropriate because at that age they should be learning how to pursue science and not how to spend money. Meanwhile, older scientists feel ignored. I don?t even mention pathological situations, which also occur, where project heads don?t apply for money for themselves but submit projects for their PhD students.

?Straw men? in science?!

Yes, because the competition in the group of PhD students seeking funding for projects is not as great, and that money is therefore more certain.

The emphasis on funding young researchers is aimed at getting them to stay in Poland.

But do we really want to keep everybody, at any price? The number of PhD students has grown dramatically in recent years, to more than 35,000. Nonetheless, the percentage of doctorates earned has not changed, because doctoral studies are for many just an additional source of small income. Lots of the dissertations that are developed do not expand knowledge in the given field because they imitate what has already been done.

The lead author of the article published in Science Translational Medicine which I mentioned is a PhD student of Dr Chowdhury?s. It was one of three of his works?all of which were published in important journals?which made up his doctoral dissertation on repairing damage to DNA following radiation treatment. These articles, based on research conducted for millions of dollars, are cited and extend scientific knowledge. But the author devoted seven years to his doctorate! That was all he did. He didn?t teach, he didn?t direct research projects, he didn?t file accounts or order reagents, because those things were handled by other specialized team members. In Poland all of those things are the task of the PhD students, so they are doing really well if they have 30?40% of their time left over for research work.


Dr Wojciech Fendler by One HD

You weren?t tempted to leave Poland?

Many times! But in Poland I am an independent researcher, I can obtain funding, I have family and friends here. I am preparing my first application for a grant from the European Research Council. Should I leave that behind? Besides, if I chose to lead a contented life at a well-respected research institution in the United States or Western Europe, I could only conform to the system, because everything there is more or less already in place. Here I have the opportunity, together with colleagues, to build something good. Maybe not huge at first, but along our own lines.

As in the project for improving neonatal care which you were involved in when you were a student, which reduced the infant mortality rate in Łódź province to 0.4%?

The idea was raised by Prof. Andrzej Piotrowski. My mother, who for many years headed the European Institute in Łódź, offered lots of advice on how to complete the application for an EEA grant under the Norwegian Financial Mechanism. The bursar?s office at the university handled the bureaucracy for the project. It took us two tries, but we raised the funds to outfit all of the neonatal wards in the province (including those in smaller institutions, where children generally have a lower chance of survival in the case of problems) with basic equipment for restoring vital functions in newborns. More advanced equipment was supplied to specialist hospitals where intensive care was possible. Hundreds of people were trained: nurses, midwives, doctors. We don?t claim that in fact it was because of this project that the infant survival rate rose, but I still feel that this was money well spent. It was invested at every level of healthcare, and thanks to the training new staff could learn how to operate the equipment from experienced predecessors.

As in the case later with the register of monogenic diabetics, we made something out of nothing?this awareness probably gives me the greatest satisfaction. So, to answer your question about the temptation to leave Poland, that no longer affects me?particularly since the model of cooperation of my department now is that we consult in the team on data transmitted from numerous institutions, including foreign ones. In an era of fibre optic communications, it?s no problem to establish contact with a centre like ours, which through a combination of clinical, molecular and statistical knowledge is capable of conducting any analysis. And because maintaining permanent contact is not an issue, research can be done anywhere. Including Łódź, where I have the opportunity to build a world-class team pursuing molecular medicine.

Have you paid a price for that commitment?

Probably the price that I don?t have enough time for everything. Also because my wife was working on completing her specialization in radiotherapy, so far we have not yet decided to have a child. We don?t even have a dog, because it would have to sit at home alone all day. By necessity, we had to give up a lot of social life and sports. There was simply a time?it won?t always be that way?when sacrifices had to be made, working 12 hours or more nonstop.

Anyone who wants to achieve something will say the same: if you want results, don?t count the time. You have to decide on that kind of life consciously, and it also impacts your relationships. My wife Justyna understands me when I?m frantically finishing a project, and I understand her when she comes home from tough rounds at the hospital.

Do you remember the hardest times, when you were drowning in numbers and stacks of paper?

Yes, but it didn?t involve work. It was the discussion I had with Prof. Młynarski, when I told him that I wasn?t going to start a specialization because I wanted to handle exclusively research. It was also tough a few years earlier when I ended my cooperation with Prof. Piotrowski, as I decided that I would practise molecular medicine and not neonatology. The need to close out a certain phase and take a risk was the hardest. Every time I was worried about stepping out from under the other person?s sheltering wing, but I was pushed ahead by the desire to test myself in a new situation?the internal confidence that I wanted to do something more, or different than I had done before.

I try to keep a broad outlook. I encourage my undergraduates and doctoral students to talk to other people, seek out interesting results, keep up-to-date on the scientific literature. And to be prepared at any time to discuss what they?re working on.

But why?

Because if they happen to be in the lift at our clinic and bump into the minister of health or an investor like Elon Musk from Silicon Valley, they could without hesitation say, ?I have a concept to pursue in diagnosis of ovarian cancer which could save the lives of three thousand Polish women a year, and I need five million zlotys to test it.? They may not get the money, but they have a clear message on what they?re doing, why it?s important, what they need. In short, what it?s all about?what is the point of their work and all the related endeavours.

WOJCIECH FENDLER, PhD (born 1982 in Łódź) is the head of the Department of Biostatistics and Translational Medicine at the Medical University of Łódź. He is a winner of the FNP programmes START (2012, 2013), INTER (2014), IMPULS (2014) and MENTORING (2015). In 2016 he was chosen for the Young Scientists Academy of the Polish Academy of Sciences.