We can fix genes, but I wouldn’t want to tamper with nature,” says a globally esteemed biologist Josef Jiřičný

At the age of eighteen, he emigrated to England, studied chemistry in Birmingham, and earned his doctorate in London. Although originally a chemist, he gradually shifted his focus to the research of cancer biology and molecular DNA biology. He discovered proteins that prevent the onset of hereditary colorectal cancer. In addition to the United Kingdom, he worked in Italy and Switzerland. An esteemed molecular biologist, an expert in cancer biology, and former director of the Institute for Molecular Cancer Research in Zurich, professor Josef Jiřičný visited his homeland after some time. He came to the International Clinical Research Center (ICRC) in Brno on the occasion of evaluating scientific teams.

You are a member of the European Molecular Biology Organization and the scientific society Academia Europaea. Since the age of 18, you have been living in London, studying in Birmingham and London, and working in Basel, Switzerland. A few years ago, you became a member of the International Scientific Council of Masaryk University. What differences do you see in science here and abroad?

I believe that the average quality of university education in the Czech Republic is very high. In the Czech Republic, the study lasts for five years, and students gain not only theoretical but also practical knowledge. In the British system, a graduate with good results can go directly to a Ph.D. program. However, during bachelor’s studies, one doesn’t gain much practical experience. Here, because the study duration is longer, students acquire many more practical skills. In England, where I studied, there are significant differences in the level of individual universities. In the Czech Republic, the basic curriculum taught at MUNI, UP in Olomouc, or anywhere else is very similar. We have state-prescribed standards, ensuring that a master’s graduate in one field in Prague has comparable knowledge to a master’s graduate in the same field in Hradec. In Britain, only a handful of talented high school students get into certain universities; subsequently, they are taught by world-class experts, but significant demands are placed on student performance. They leave with a unique education, incomparable to other British schools. In the Czech Republic, basic higher education is considered equivalent.

You emigrated to Britain in 1969, shortly after graduating from high school. Did you have plans for the direction you wanted to take or which field to study?

I’m quite a specific case in this regard. I fled to England when I was eighteen, and then I worked for a year. I couldn’t go to university immediately because I couldn’t speak English, and I didn’t have the financial means. Therefore, I had to choose from universities where no entrance fees were required. When they offered me a place at the University of Birmingham, I was happy. While the school wasn’t the best of the best, I could study there for free. After that, it was up to me to figure out how to handle it.

What was the period immediately after emigration like?

For the first nine months, I worked at the cinema. In England, they granted me a work permit right away as an asylum seeker, which was very generous of them. I worked in unskilled professions, so although I wasn’t initially surrounded by intellectuals, I learned to speak. Later, I worked in SOHO, which was an incredibly interesting part of London! I also sold suitcases and handbags for a while. In 1969, I started studying at the university, but I still had to earn extra income. My older sister (famous architect Eva Jiřičná) also helped me a lot.

Was molecular biology not a clear and primary choice?

I left the Czech Republic shortly after the Russian invasion; the whole world was in turmoil. We didn’t know if we would still exist in a year. Before the Russians came, my biggest life problems were my rock ‘n’ roll band and my beautiful girlfriend. I didn’t think much about the future. I always wanted to be a doctor. However, I knew that I didn’t have a chance to get into medicine in the Czech Republic; due to my involvement in rock ‘n’ roll, I wasn’t the best student. Subsequently, I found out that it wasn’t an option for me in England either, as they only select a handful of the best students for medicine.

Were you afraid that your knowledge wouldn’t be sufficient?

Yes, because our education is structured differently. In high school, we cover around twelve subjects, learning a plethora of things that we won’t need in our future lives, but we don’t have a chance to deepen our knowledge in a specific field. The system is different in Britain. Until roughly the age of our ninth grade, students have eight subjects, and then they focus only on the field they have chosen. So, if you want to study medicine, you logically concentrate on chemistry, biology… And over the three years of specialization, you gain not only theoretical but also practical knowledge. I, however, didn’t have that. I was thinking about where to go and thought, the closest field to medicine is chemistry… I gradually shifted towards chemistry with biological applications. During my second postdoc, I focused on DNA synthesis, which was unique at that time. Har Gobind Khorana had just won the Nobel Prize. I found myself in a situation where biologists came to me with requests for various oligonucleotides, short pieces of DNA used for biological experiments. I didn’t understand those biological experiments; I was a chemist. Still, I thought it would be interesting… Chemistry can play a crucial role in the field of biology, after all. I approached my chemistry professor, who had contacts at the Imperial Cancer Research Institute, and he recommended me to the Institute as a chemist who wanted to learn about biology. So, I gradually immersed myself there. I found that the only obstacle for a chemist in biology is essentially the terminology. Suddenly, I was learning very quickly, understanding biochemistry, molecular biology… And then I got the opportunity to establish my own research group in Basel. I don’t know how it happened. I guess I’m just lucky in life.

I believe that significant knowledge and abilities contributed to that luck! Did you decide on Switzerland immediately?

When I was working in the lab in London, the phone suddenly rang, and an American voice on the other end said that he was taking over an institute in Switzerland and looking for a group leader. I didn’t know who he was, and I hadn’t even heard of the Friedrich Miescher Institute for Biomedical Research at that time. By then, I already had an offer for a position as a chemist at the European Molecular Biology Laboratory in Heidelberg. I met with the American in London; I took him to Windsor Castle. We barely spent four hours together, and he offered me the position. When I returned home, my wife told me I was crazy. (laughter) We were already prepared to move to Heidelberg. However, in Basel, they promised to build an entire laboratory and fill eight positions for me. Additionally, Switzerland was a neutral country, so we thought it would be better to go there with the family. In the end, I spent seven years there.

What would you consider the peak of your career? Was it the period in Basel and the research on colorectal cancer?

During the research in Basel, we discovered three proteins that became the focus of our subsequent work. However, we didn’t have any specific ideas about their effects. We knew their biochemical characteristics, but we had no idea if they would ever be relevant to any disease. In 1993, an article appeared in which a geneticist working at the dental faculty found a connection between a specific phenotype in patients with hereditary colorectal cancer and the activity we were measuring. Our substrate was biologically identical to his phenotype. Another scientist then contacted us, mentioning that the same phenotype was present in yeast, with which he worked. However, he already knew the specific defect in the genome that these yeasts had. Coincidentally, that defect was precisely in the genes encoding two of our proteins. It was the work of about ten research groups, and suddenly everything crystallized within three years. We discovered proteins crucial for maintaining the stability of our genome, and when mutated, they cause colorectal cancer.

Your research on colorectal cancer involves DNA errors in human cells and, consequently, hereditary predispositions to colon cancer. How is the diagnosis of these predispositions currently available?

People with a genetic predisposition have been identified. Colorectal cancer is fortunately highly preventable. If we know through endoscopy that this disease runs in the family, we can conduct a genetic diagnosis and identify descendants who inherited the mutation, monitoring them annually. These tumors develop as small polyps that are not yet dangerous. It takes five to seven years for them to turn into cancers. If polyps are removed from the colon in time, colorectal cancer does not develop. Endoscopy also prevents sporadic colorectal cancer. If each of us undergoes endoscopy every 5 to 7 years from the age of fifty-five, we could significantly reduce the incidence of this cancer, along with lifestyle changes.

Why do you think our region is plagued by such a high incidence of this cancer? Is it our lifestyle? Do we really live so much unhealthier compared to other countries?

In my opinion, yes. If I look at the local restaurant menus, I see nothing but meat, sauces, dumplings… No vegetables. I can’t get any fresh salad for lunch… It’s missing here, the habit of incorporating a bit of vegetables with every meal from childhood. Also, there’s the lack of physical activity; considering the average time we spend sitting at work and then at home in front of the television…

I dare to claim that this is perhaps changing with our generation, that despite many of us having sedentary jobs, we still know that we need to compensate for it somehow a few times a week…

It’s a matter of health education. Now, in my old age, I’m improving my French, so I started listening to French radio. There, after the news, there’s a short health education segment directly from the Ministry of Health on various topics, whether it’s about COVID or broccoli in the diet… The population receives information regularly and completely passively. Of course, I can’t judge because I don’t actively follow Czech media.

Within your research, you discovered proteins that can repair a DNA error, thereby preventing the development of genetically conditioned tumors. How far are we from practically correcting such “repairs”? Meaning, being able to fix this “error” in our descendants?

Well, it’s already possible… It’s just currently illegal. The technology to modify our genome exists; we have the ability to develop a human from a single cell of one parent, and it’s in these cells that a genetic defect can be modified. However, this technology is not one hundred percent effective. It means that while we might correct that mutation, the process could also change something else somewhere else…

And at what stage of development would it be possible to detect this?

That’s very difficult. It would be possible to detect it, but… Imagine this. You work with one cell, then let that cell multiply, perhaps into four cells. Then you take one of those cells and sequence its DNA. If you find only the correction there, you can let the remaining three cells create a whole embryo. However, you might overlook another mutation, and so it could happen that you let a cell develop into a child with a genetic defect. Then comes the ethical problem – should you let the child survive? There is also the danger of human cloning. This is how the famous sheep was cloned in England… That’s why ethical rules must be very rigid. Most people have that boundary set, but there will always be individuals who will do anything for money. So yes, we can fix this genetic defect, but currently, it is not allowed.

And personally, would you be in favor of putting it into practice?

Answering that is incredibly difficult… When a person empathizes with a family where an analysis of amniotic fluid shows that the child will suffer from Down syndrome… And then you have the option of abortion or raising a child who will simply be different. People with Down syndrome can still lead a happy life, albeit different. However, when you have a child born with a severe defect, such as having trouble sitting, ethical questions are far more complicated. We don’t know how the child feels, how it perceives, whether it can be happy… And then there’s the effect that raising the child has on the parents. Their lives are completely turned upside down, the chances of improving the child’s condition are minimal… So defining at what point genetic correction is possible or even recommended is so incredibly difficult. I would lean more towards not doing it. I know that there are many people who really want a child and are willing to take the risk that it may be sick, but on the other hand, the world is full of children who need parents and don’t have them. I would much rather see more adoptions than playing with nature and changing the laws of life and death.

Is this your first visit to the International Clinical Research Center (ICRC)?

Yes. I have participated in the evaluation of scientific teams here once, but that was during the COVID era, so it was conducted via Zoom. This is my first personal visit.

How do you evaluate ICRC based on your initial impressions?

So far, I haven’t had the opportunity to explore all areas. I am primarily familiar with the laboratories located in the university campus, and they have made a good impression on me.

If you compare ICRC with other international research institutions you have come into contact with during your professional career, how do we stand?

That is a very difficult question. As an evaluation committee, we currently have difficulty understanding its functioning. ICRC is spread between St. Anne’s Hospital and the Faculty of Medicine, as well as other faculties and institutions. Its operation is, one could say, almost virtual. It is clear with clinical laboratories, as they are part of the hospital, but for the rest, we are confused – who is the employer, a legal entity – is it ICRC, the hospital, or the faculty?

And concerning the comparison of our scientific teams, how do you think we fare compared to foreign ones?

From what we have seen so far and the documentation available to us, we believe that the scientific standards in the majority of research teams are comparable to Western institutions. I was very positively surprised.

The International Clinical Research Center (ICRC) is a joint facility of St. Anne’s University Hospital and the Faculty of Medicine at Masaryk University.