Whom we help| Jiří Bartek’s team| Swamping researchers with paperwork doesn’t...

Jiří Bartek: Swamping researchers with paperwork doesn’t help anyone

“All researchers can gain experience abroad at present. Not all of them use the opportunities sufficiently, though,” claims Jiří Bartek. He spends most of his time abroad. He has been at the helm of the Cell Cycle and Cancer lab of the Danish Cancer Society Research Center in Copenhagen, Denmark for the last twenty years. He also keeps coming back to Olomouc. He is currently the most cited Czech scientist and has summed up his work in several hundred publications.

He has received support from The Kellner Family Foundation for his long-term research into the possibilities of personalized treatment of prostate cancer, which is targeted at the mechanisms that preserve genome integrity. Ten researchers and lab assistants are involved in the project at three sites: at the Institute of Molecular and Translational Medicine of Palacký University in Olomouc, the Institute of Molecular Genetics of the ASCR in Prague, and the Copenhagen-based Danish Cancer Society Research Center. The principal objective is seeking and experimentally verifying new strategies for the targeted killing of the human prostate carcinoma cells.

They say you are the only Czech scientist with a shot at winning the Nobel Prize – is this largely due to the fact that you work abroad?
Being abroad has certainly greatly benefited my work and what I’ve been able to achieve. The competition is much tougher abroad, but they also show more respect to top scientists and treat them accordingly, which in turn yields superior results.

Is it therefore easier for a researcher to pursue a career abroad rather than building a respected lab in the Czech Republic?
I wouldn’t dare say it’s easier in any respect. All scientists have had opportunities for pursuing a career abroad or at least for learning as much as possible and putting it to use at home for almost a quarter-century now. Not all of them use the opportunities sufficiently though. At the same time, the conditions for building excellent labs in our country are very good now in terms of infrastructure – new institutions and instrumentation. Salaries have improved too, mainly thanks to the European Union funds. The grant support system is lagging behind though.

Is, then, the idea that scientific environments are comparable everywhere in the globalized world at odds with reality?
There’s no question that research in oncology and molecular biology in the Czech Republic has progressed to a higher and far batter level since the Velvet Revolution (in 1989). However, we still have a long way to go to match the most developed countries with an extensive tradition. In my opinion, faster progress in this area is not just a matter of greater financial support (although it obviously is crucial), but also a matter of organization, for example, cutting down on the huge bureaucratic load scientists often face due to administrative requirements and measures, which are addressed much more simply and efficiently in more developed countries. This is another area where we have a long way to go and many problems to solve; sadly, a lot of them are artificial and as such they needlessly reduce the amount of time scientists can use in creative research, undermining the effectiveness of research work, and hindering the faster application of new knowledge in oncology. Last, but not least, we need enthusiastic and erudite young people to develop tumor research further in this country.

Does the government offer young people sufficient motivation? How do you rate researchers’ social status in the Czech Republic?
This question is related to the previous one. I think, however, that societies in advanced countries with democratic traditions hold science and researchers in greater esteem than in our country. Besides that, the basic research funding system is excessively centralized here. For example, in Denmark, a small country with half the population of the Czech Republic, they have at least five big foundations and sources of grants for research, which makes for greater objectivity in addition to having international experts assessing grant projects. The increasing share of support for research from non-governmental foundations such as The Kellner Family Foundation is one of the springs of hope for the future in this respect.

Does the research that you received the grant for focus solely on prostate cancer, or is it applicable to tumor treatment in general?
Simply put, we are looking for such molecular changes in tumors, i.e. differences from normal cells, which allow the tumor to grow and which the tumor depends on. These properties are beneficial for the tumor, but they are also its weakness, a potential Achilles’ heel of the tumor that can be used in treatment. Our project supported by the Foundation centers on prostate cancer, because it constitutes a major social problem due to the increasing age of the population. Still, our research approach is to obtain results applicable to other types of tumor as much as possible. For example, prostate cancer and breast cancer share the basic traits of malignant transformation and also a significant influence of steroid hormones and their receptors. Prostate cancer involves androgens, and breast cancer involves estrogens.

You suggest that drugs could be tailor-made in the future. How would they work?
Yes, examples exist of drugs tailored to a specific group of patients within the large number of people suffering from the same cancer diagnosis. The approach is again based on the above molecular and genetic differences between normal cells and cancer cells. In this specific case, it is also based on the fact that a certain abnormality contributing to tumor growth occurs only in some of the patients who share the same type of tumor, whereas in other patients with the same neoplastic disease, the tumor has evolved due to some other genetic and functional changes, albeit in the same organ and cell type. Simply put, you can imagine the principle as a table on four legs. Each leg stands for one of four genes that complement each other. One of the genes is either defunct or, on the contrary, abnormally highly active in the tumor in a specific patient, making the process abnormal and causing the tumor to proliferate uncontrollably. But the table still has three legs, enough for it to stand. However, the table is vulnerable now, in the sense that the three remaining legs are indispensable. If we understand the mechanisms and have a drug that can block one of the three remaining functions, we will cause the tumor to collapse. Figuratively speaking, we cut another leg, and the table cannot stand on two legs. The important thing is that normal, non-tumor cells in that patient are not seriously damaged. The administered treatment can block the particular function of certain normal cells too, since but the failure of the first gene (the notional first leg of the table) occurs only in the tumor cells, normal cells in that patient still have at least three legs working. For another patient, though, we have to seek another drug tailored to the abnormalities in their specific tumor.

Would tailor-made drugs bring nothing but benefits?
The particular drug is only administered to those patients in whom it stands a chance of affecting the tumor. This way we avoid drug wasting medication and also the unnecessary treatment of other patients whose tumors the drug will not affect and may even cause undesirable side effects. The problem is that such personalized approach requires more sophisticated and costlier molecular diagnostics to determine the condition of genes. There are hundreds of such genes in humans, although some are more important than others and not all of them have to be tested. Another problem is that certain combinations of genetic changes can be rare, so there are ‘only a few’ of such patients, and the production of the drug therefore would not be worth the investment for pharmaceutical firms. Yet another general complication is what is called tumor heterogeneity, meaning that one tumor is composed of cells that may have undergone different genetic changes. This is why just some (and not all) of the patient’s cells respond to the particular drug administered. The surviving cells can cause a relapse. Still, despite these complications, the improving understanding of cancer cell biology and pathology together with the increasingly sophisticated research and therapy apparatus offer a good chance of improving outlooks for oncology patients in the future. It will not be an easy path to follow by any means though.

So when could be the first time a specific patient experiences the outcomes of your research?
The timeframe for applying new approaches to treatment depends on circumstances. Usually, the entire process, including the official approval of the new drug, takes several years and is incredibly costly. But a new promising drug can find its way to patients earlier in two ways. One is via clinical trials where the efficacy of a new drug is compared to the effects of the standard treatment procedure in a limited group of patients with a certain type or stage of the disease, under strict monitoring by a team of doctors and researchers. The other way is cancer treatment using an already proven drug that has been approved for clinical use, but for a different disease. This other option builds on latest research demonstrating the positive effects on a certain type of neoplastic disease of a drug that has only been used, say, for epilepsy so far. We seek to use both approaches, including the subsequent stage of our project supported by the Foundation.

What makes a renowned researcher decide to apply for such a grant?
The reasons for trying to obtain research subsidies from the Foundation are obvious. Research, and not just in biomedicine, is very costly now, and the sources of funding are limited in our country. In addition, the world of science has been severely hit by the global financial crisis, and so raising sufficient funding has become more difficult, especially for large labs such as ours. But I have to keep applying for grants in Denmark as well. The process is almost eternal, and if you are not writing a new grant application, you are writing interim and final reports for the projects and grants you have been awarded. This takes an incredible amount of effort and time that researchers could use better. That said, suggesting a better alternative is not easy. Countries such as the U.S., U.K. and Germany use a special system of subsidizing elite scientists without the need to apply for grants. This support is granted on the basis of excellent results of selected researchers and their labs, and the high standard of their scientific achievements and their publications in first-class journals gives a good guarantee that these teams will produce excellent new results for at least the next five years. The labs are evaluated throughout the period. And if their research is still high quality, they get subsidies for the next five years, again without having to apply for grants. The amounts are often incomparably higher than our grants. They have realized by now that swamping elite researchers with paperwork is just a waste. That will give the country nothing. They will gain so much more when researchers can dedicate their time and energy to their jobs.

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